Cobbers on the Brain – Page 3 – Student Commentary on the Neurological Sciences

Brain-Body Connection in Obesity

Posted on April 19, 2025 by hdahlsei / 0 Comment

Recently, hypothalamic inflammation has been linked to obesity. The evidence suggests a high fat diet leads to brain inflammation, causing the uncoupling of food intake and energy expenditure, which leads to overeating and obesity [1].

Normal Metabolic Feedback Loop

In healthy brains, the hypothalamus regulates energy and metabolism successfully. Insulin and leptin anorexigenic (“don’t eat”) signals are proportionate to fat cell mass. This means the brain tells the body to only eat what it needs based on how much energy it has spent [1].

More specifically, AgRP neurons are inhibited. These are the neurons telling the body to eat more. Additionally, POMC neurons are stimulated, which sends a “don’t eat” signal to the body. When this is working under normal circumstances, there is a balance between food intake and energy expenditure [1].

Obesity and Metabolic Syndrome

However, when a high fat diet (especially saturated fatty acids) causes hypothalamic inflammation (specifically due to increased JNK and IKK inflammatory mediators), a couple things happen. There is resistance to insulin and leptin signaling. Which essentially means the brain is not listening to these signals. Also, food intake and energy expenditure is uncoupled. This means the same metabolic feedback loop described above doesn’t work right [1].

AgRP neurons are not inhibited, causing too much excitatory (“eat”) signalling. Additionally, POMC neurons are not stimulated, causing not enough inhibitory (“don’t eat”) signalling. This means the brain tells the body to eat, regardless of how much energy is spent, or how much fat cell mass there is. The body eats too much relative to how much energy is spent, making these processes uncoupled and unbalanced [1].

Long Term Effects

The immediate effects of a high fat diet and brain inflammation described above are dysregulating, but there are also impacts with a long term high fat diet.

Alteration in synaptic plasticity for hypothalamic neuronal systems
Apoptosis of hypothalamic neurons and reduction of synaptic inputs
Increased microglia in the hypothalamus, causing more inflammation
Increased astrocytes in the hypothalamus, causing more inflammation
Impacts on the blood-brain-barrier’s integrity
Places in the brain and body that the hypothalamus projects to are also impacted. This includes: the rostral ventrolateral medulla, NTS, and dorsal motor nucleus of the vagus nerve in the hindbrain [1].

Interoception

So, in obesity, the signals between the brain and body are off balance, causing overeating and obesity. Interestingly, there is another cause for brain and body disconnect that could potentially lead to overeating and obesity as well. In this instance, it is not inflammation that causes obesity, but a lack of interoception ability. Interoception is:

The perception of internal signals from the body [2]
The ability to sense, interpret, and integrate signals originating from within the body [3]
Signals from internal organs to the brain
The ability to keep the body in balance
Examples include being able to feel: hunger, thirst, cold, warm, tired, racing heart…

The main way the brain is connected to the body in order to send these signals is the vagus nerve. It is a major brain-body communication pathway, and has sensory neurons that innervate internal organs [3].

Deficits in Interoception

Some people are better at sensing these brain-body communication signals than others. One way this is measured is a task to count your heartbeat without using your fingers to find your pulse. People who have worse interoception are those with autism, ADHD, eating disorders, and depression [2].

Interoception and Obesity

Deficits in interoception are associated with relying less on hunger and satiety signals to determine when to eat. Deficits in interoception are also linked with a higher BMI. However, scientists studying this are unsure of the direction or causality of the issue. Meaning, does interoceptive deficits cause increased BMI, or are interoception deficits a result of an increased BMI? [4]

So, we know a high fat diet, leading to inflammation, causes obesity. But we also know deficits in interoception are linked to obesity. It is important to understand these links to obesity in order to make the healthiest choices for your own brain and body.

References

[1] Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. Journal of Clinical Investigation, 127(1), 24–32. https://doi.org/10.1172/jci88878

[2] McDonough, M. (2024, June). Making Sense of Interoception. Harvard Medicine Magazine. https://magazine.hms.harvard.edu/articles/making-sense-interoception

[3] Robinson, E., Foote, G., Smith, J., Higgs, S., & Jones, A. (2021). Interoception and obesity: A systematic review and meta-analysis of the relationship between interoception and BMI. International Journal of Obesity, 45(12), 2515–2526. https://doi.org/10.1038/s41366-021-00950-y

[4] Robinson, E., Marty, L., Higgs, S., & Jones, A. (2021). Interoception, eating behaviour and body weight. Physiology & Behavior, 237. https://doi.org/10.1016/j.physbeh.2021.113434

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The U.S. Diet’s Impact on High Obesity Rates

Posted on April 15, 2025 by klind2 / 0 Comment

Obesity is common in the United States, with more than 1 in 5 people in the United States being obese. [1] The figure below represents that some areas of the U.S., such as the Midwest and the South, have even higher rates of obesity.

Figure 1: Obesity prevalence in the United States in 2023 [2]

United States has one of the highest rates of obesity, but it is a problem in other areas of the world as well. The map below portrays the rates of obesity across the world in 2016.

Figure 2: Global rates of people who are overweight or obese in 2016 [3]

Yet, what do we know scientifically about obesity and Metabolic Syndrome? Each area in the world has a different diet, so how does the food commonly eaten in the United States contribute to the high prevalence of obesity?

What’s Happening in the Body During Obesity

The hypothalamus, a region in the brain, is responsible for our appetite and eating behaviors. There are AgRP neurons and POMC neurons inside the hypothalamus. The AgRP neuron signals tells us we’re not full, while POMC neuronal signals tells us we’re full. The yellow AgRP neurons will activate the blue MC4R neurons, the “eat” neurons so we keep eating, while the POMC neurons will inhibit the MC4R. In other words, the POMC will make sure the “eat” neuron, the MC4R neurons, will stop telling us to eat.

Figure 3: Neurons related to full or hungry feelings [4]

However, in obesity and metabolic syndrome, this process goes out of balance. The AgRP neurons will continue activating the eat neurons, and the POMC neurons won’t tell us we’re full, so we end up eating more than we should because we don’t feel full.

Impact of a High Fat Diet on our Bodily Processes

Obesity also causes low-grade inflammation throughout the body that can disrupt important processes, including neurons such as AgRP and POMC. Some of this inflammation can arise from a high fat diet, even within a few days after a high fat diet. This diet can cause acute inflammation in the hypothalamus. [5] Chronic consumption of a high fat diet will perpetuate the inability to feel full when you’re supposed to.

A high fat diet is when 30-60% of calories consumed are from unsaturated and saturated fats. [6]

Saturated fats trigger inflammatory pathways, and decrease insulin and leptin sensitivity, something that helps us break down food into nutrients. Meanwhile, unsaturated fats help increase insulin and leptin sensitivity which helps us break down our food into their nutrients. [8] Saturated fats are harmful in large amounts; unsaturated fats are helpful!

A Reflection on Common U.S. Foods

Considering that foods that are high in saturated fats such as fried food, red meat, chips, vegetable oil, and dairy products are in the everyday diet for a lot of Americans, it’s no wonder the obesity rate is so high in the U.S. compared to other countries. Especially considering our large portion sizes that encourage over-eating.

Food is not the enemy, neither is saturated fats in low amounts, but it’s important to have balance in our diets to ensure a healthy life. A hamburger and fries won’t completely harm your body, but it’s beneficial to limit the consumption of these “bad” foods and balance it with healthy foods.

References

[1,2] CDC. (2024, September 12) Adult Obesity Prevalence Maps. https://www.cdc.gov/obesity/data-and-statistics/adult-obesity-prevalence-maps.html

[3] Ritchie, H., Roser, M. (2017, August) Obesity. Our World in Data. https://ourworldindata.org/obesity

[4,5] Jais, A., Brüning, J. C., (2017). Hypothalamic inflammation in obesity
and metabolic disease. The Journal of Clinical Investigation, Vol. 127(1): 24-32. doi:10.1172/JCI88878.

[6] Willebrords, J, et. al. (2015). Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research. Progress in Lipids Research, Vol. 59: 106-125. https://doi.org/10.1016/j.plipres.2015.05.002

[7] YMCA. (2022, June 1). Four Myths About Eating Fats. https://lafayettefamilyymca.org/myths-about-eating-fats-2/

[8] Jais, A., Brüning, J. C., (2017). Hypothalamic inflammation in obesity
and metabolic disease. The Journal of Clinical Investigation, Vol. 127(1): 24-32. doi:10.1172/JCI88878.

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ADHD medication addiction properties

Posted on April 15, 2025 by smtesa / 0 Comment

Figure 1: The Addiction Potential of ADHD Medications
Created by Sharleen Mtesa. This image shows the risk of addiction associated with ADHD medications when misused.

Psychostimulants like nicotine, cocaine, and amphetamines—think methamphetamine, MDMA, and even ADHD meds like Adderall are often seen as the bad guys in the world of substance use disorders. And they are, in many ways, wreaking havoc on both physical and mental health. But what’s even more concerning is how these drugs impact the brain’s ability to adapt and rewire itself. When the brain’s natural ability to learn and adjust gets disrupted, recovery becomes that much more challenging.

Therefore, researchers have turned their attention to metabotropic glutamate receptors (mGluRs)—crucial players in learning, memory, and brain plasticity. Emerging evidence suggests that mGluRs play a central role in how the brain rewires itself in response to repeated drug use [1]. And this opens the door to potential therapies that could help us manage, or even prevent, the long-term effects of psychostimulant use disorders (SUDs).

The Highs and Lows of ADHD Meds: How Amphetamines Hack Your Brain

Let’s zoom in on one class of psychostimulants: amphetamines. You’ve probably heard of Adderall and Vyvanse, common medications used to treat ADHD. While they are effective tools for improving focus and attention, they come with a more complex story. Chemically, amphetamines are closely related to street drugs like meth and cocaine, which makes them especially powerful in the way they affect the brain’s reward system.

Not only do they boost dopamine and glutamate levels, but they also interact with Group I metabotropic glutamate receptors (mGluRs) [2] —specifically mGluR1 and mGluR5. According to the paper “A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder,” shows that these receptors become more active and start to reorganize in the brain [1]. And the medial prefrontal cortex (mPFC)? well this reorganization is especially important in the medial prefrontal cortex, which plays a key role in decision-making and cognitive functions. Changes in the mPFC can affect attention, impulse control, and overall thinking, helping explain why long-term stimulant use impacts these abilities.

So what’s the fallout from all this rewiring? When the mPFC increases its mGluR5 receptor activity, it makes the brain more likely to link the drug with pleasure, long after the first dose. This explains why people who misuse prescription stimulants can develop cravings and get hooked. The addictive potential is real, and understanding these effects is crucial, especially when it comes to medications.

ADHD Medications: Powerful Tools or Potential Pitfalls?

ADHD medications like Adderall, Vyvanse, and Ritalin are often life-changers for people struggling with focus, attention, and impulse control. These medications work by boosting levels of dopamine and norepinephrine [3] in the brain, allowing individuals to stay on task, manage their emotions, and excel in school or at work. For those with ADHD, these medications can be a game-changer, providing the structure and focus they need to thrive. But here’s the twist, when these same medications are misused, whether to stay awake, cram for exams, or chase a euphoric high, they hijack the brain’s reward system.

What Are Adderall and Vyvanse?

Adderall is a combination of two stimulant drugs: amphetamine and dextroamphetamine. By increasing the levels of dopamine and norepinephrine in the brain, Adderall helps improve focus, attention, and impulse control. The immediate-release version typically takes about 30-60 minutes to kick in and lasts around 4-6 hours, while the extended-release (Adderall XR) form provides longer-lasting effects of 10-12 hours.

Vyvanse, on the other hand, contains lisdexamfetamine, which is a prodrug. This means the body must metabolize it into its active form, primarily in the liver. It takes a bit longer to kick in, usually around 1-2 hours, but its effects can last up to 12-14 hours. Because Vyvanse is a prodrug, it has a smoother release, which might make its effects feel less intense compared to Adderall

The Dopamine Pathway: The Power and Pitfalls of ADHD Medications

One of the core reasons why ADHD medications like Adderall and Vyvanse are so effective is because they increase dopamine levels, especially in areas of the brain like the prefrontal cortex and striatum.

How it works:

Dopamine is released into the synapse. Under normal conditions, dopamine is reabsorbed by the neuron through a process called reuptake. But stimulants like Adderall and Ritalin block the dopamine transporter (DAT), preventing dopamine from being reabsorbed. This causes dopamine to accumulate in the synapse, enhancing focus, attention, and motivation.

Key Areas Affected:

Prefrontal Cortex: This region controls attention, decision-making, and impulse control.
Striatum: This area is involved in reward, motivation, and habit formation.

The Norepinephrine Pathway: Fueling Focus and Alertness

In addition to dopamine, these medications also boost norepinephrine, another neurotransmitter that’s important for alertness and focus.

How It Works:

Norepinephrine is released from nerve endings and binds to receptors that help increase alertness and focus. Stimulants like Adderall and Vyvanse block the norepinephrine transporter (NET), preventing norepinephrine from being reabsorbed. As a result, norepinephrine stays active in the synapse for longer, helping to maintain focus and attention.

Key Areas Affected:

Locus Coeruleus: This region regulates arousal, stress response, and alertness.

Figure 2: Stimulant Mechanisms of Action in ADHD Medications
This figure shows how ADHD medications like amphetamine (AMPH) and methylphenidate (MPH) increase dopamine (DA) and norepinephrine (NE) levels by affecting the dopamine transporter (DAT) and norepinephrine transporter (NET). AMPH and MPH promote the release of these neurotransmitters through DAT phosphorylation and reverse efflux, inhibiting reuptake and enhancing synaptic activity. [4]

Why This Can Lead to Addiction

While these medications are incredibly helpful for those with ADHD, they can also become addictive if misused. When Adderall or Vyvanse is taken for reasons other than prescribed—like to stay awake longer, study harder, or experience a euphoric high, the mesolimbic dopamine pathway, also known as the reward pathway, becomes activated. This pathway connects the ventral tegmental area (VTA) to the nucleus accumbens, creating powerful feelings of euphoria.

As a result, the brain starts to reinforce this behavior, making the individual crave more of the drug. Over time, this cycle of use and reinforcement increases the risk of addiction.

Figure 3: This figure highlights the brain areas impacted by ADHD, including the prefrontal cortex, basal ganglia, limbic system, and reticular activating system. Each area plays a key role in attention, behavior, emotional regulation, and impulse control. In ADHD, deficiencies in dopamine lead to symptoms such as inattention, impulsivity, emotional volatility, and hyperactivity. [5]

The Bitter Aftertaste of a Sweet Fix

So, here’s the bottom line: Adderall and Vyvanse are like superheroes for people with ADHD, helping them focus, stay on track, and crush their goals. But just like every superhero has a dark side, these medications can have unintended consequences when misused. By messing with the brain’s reward system and making it more likely to crave that dopamine rush, they can lead to some serious addiction risks. Understanding how these medications work and how they can rewire the brain will help us strike the right balance between maximizing their benefits and minimizing the risks. After all, the goal is to keep ADHD in check, not to let the medication take control of the brain’s spotlight.

Footnotes:

[1] Mozafari, R., Karimi-Haghighi, S., Fattahi, M., Kalivas, P., & Haghparast, A. (2023). A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder. Progress in neuro-psychopharmacology & biological psychiatry, 124, 110735. https://doi.org/10.1016/j.pnpbp.2023.110735

[2] Niswender, C. M., & Conn, P. J. (2010). Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annual review of pharmacology and toxicology, 50, 295–322. https://doi.org/10.1146/annurev.pharmtox.011008.145533

[3] Del Campo, N., Chamberlain, S. R., Sahakian, B. J., & Robbins, T. W. (2011). The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biological psychiatry, 69(12), e145–e157. https://doi.org/10.1016/j.biopsych.2011.02.036

[4] Dutta, C. N., Christov-Moore, L., Ombao, H., & Douglas, P. K. (2022). Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan. Frontiers in Human Neuroscience, 16. https://doi.org/10.3389/fnhum.2022.938501‌

[5] Jie, T. S. (2021, July 16). ADHD From a Scientific Point-of-View. UnlockingADHD. https://www.unlockingadhd.com/adhd-from-a-scientific-point-of-view/

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Disease/Health

Why We Never Forget: How the Brain Builds Stressful Memories

Posted on April 14, 2025 by smohame4 / 0 Comment

Artstract Created by S. Mohamed

Have you ever noticed how the most stressful or traumatic moments in life tend to stick with you forever? Maybe it was a car accident, a time where you almost drowned, or a time when you were truly afraid. While it might feel like a harsh part of life, science shows there’s a biological reason why these memories are so vivid and lasting.

The paper highlights that stressful experiences initiate powerful molecular changes in the brain that help form long-lasting memories, especially through the activation of glucocorticoid and NMDA receptors, two key players in the memory-encoding process.[1], [2].

What’s Going On in the Brain?

Understanding the relationship between stress and memory starts with the hippocampus, specifically the dentate gyrus, a region critical for memory formation. When we experience stress, like public speaking or being stuck in traffic, the brain releases glucocorticoids (like cortisol). These hormones interact with glucocorticoid receptors (GRs) and NMDA receptors, triggering a powerful signaling cascade called the ERK-MAPK pathway [2], [4].

This pathway transmits signals into the nucleus of neurons, where it leads to a specific epigenetic modification of histone proteins: a dual mark called H3S10p-K14ac. This modification essentially “unlocks” sections of DNA so that crucial immediate early genes (IEGs) like c-Fos and Egr-1 can be transcribed into genes known to be essential for memory consolidation and synaptic plasticity [1],[4].

Figure 1. Psychological stress activates glucocorticoid and glutamate pathways that converge on histone modifications to promote stress-related gene transcription.

Why It Matters to You

This isn’t just fascinating neuroscience; it has real-world implications. The research helps explain why some individuals are more susceptible to PTSD and anxiety disorders after trauma. People with heightened GR/ERK-MAPK signaling might over-consolidate traumatic memories, while those with dysregulated GABA (a calming neurotransmitter) may lack the internal braking system to moderate stress responses [3].

Interestingly, the study also shows that this specific epigenetic switch—H3S10p-K14ac—isn’t used universally across the brain. While many brain regions show c-Fos and Egr-1 activation under stress, only the dentate gyrus requires this epigenetic tag for expression, indicating a uniquely guarded gateway to memory encoding in this area [1].

Another major revelation? Glucocorticoids don’t act alone. They rapidly enhance the ERK-MAPK pathway by physically interacting with phosphorylated ERK, accelerating the stress response and memory formation. This synergy happens within minutes—much faster than traditionally believed for steroid hormones [2].

What You Can Do About It

Thankfully, our brains aren’t helpless in the face of stress. GABA plays a protective role by maintaining inhibitory control in the hippocampus. Drugs like lorazepam (a benzodiazepine) can block stress-induced epigenetic responses, while anxiogenic compounds like FG7142 can amplify them. But you don’t need pharmaceuticals to influence this system.

Natural interventions, like long-term aerobic exercise, mindfulness, deep breathing, and quality sleep all help strengthen GABAergic tone and reduce stress-induced ERK signaling. Rats with access to running wheels showed less stress reactivity in the dentate gyrus, supporting the idea that movement can help buffer the brain from chronic stress [4].

This research doesn’t just explain how stress becomes a memory, it shines a light on how we might intervene. Targeting signaling proteins like MSK1 or transcription factors like Elk-1 could pave the way for new therapies that disrupt maladaptive stress memories while preserving helpful ones [2], [4].

Figure 2. Non-pharmaceutical approaches to anxiety include therapy, alternative treatments, and lifestyle changes that support mental wellness.

The Bigger Picture

We often think of memory as a passive thing events happen, and we either remember or forget. But the truth is, our brains are constantly evaluating which experiences deserve to be encoded. Stressful or emotional events? The brain gives those the red carpet treatment [1].

This molecular precision is part of our evolutionary design it helps us learn from danger. But sometimes, the system overreacts, reinforcing painful memories and fueling cycles of anxiety or trauma. Understanding how stress, hormones, and gene expression intersect gives us the power to reshape how we respond and remember [4].

A Better Ending: Hope for Healing and Resilience

What this research really highlights is that the brain is not static. Stressful experiences can leave deep biological marks, but those marks are not unchangeable. Through interventions like regular exercise, mindfulness, and even potential drug therapies targeting specific molecular pathways, we can change how our brains respond to and store stressful experiences.

In a time where anxiety and trauma are becoming increasingly common, especially among young people, it’s empowering to know that we can take an active role in our mental health. The more we understand about the biology of stress and memory, the better equipped we are to build resilience not just by avoiding stress, but by responding to it in healthier, more adaptive ways.

Stress may be unforgettable, but so is healing. And now, we have a clearer blueprint for how to get there.

References:

Reul, J. M. H. M. (2014).
Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways.
Frontiers in Psychiatry, 5, 5.
https://doi.org/10.3389/fpsyt.2014.00005
Gutierrez-Mecinas, M., et al. (2011).
Long-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2-MSK1-Elk-1 signaling.
Proceedings of the National Academy of Sciences, 108(33), 13806–13811.
https://doi.org/10.1073/pnas.1103214108
McEwen, B. S. (2007).
Physiology and neurobiology of stress and adaptation: Central role of the brain.
Physiological Reviews, 87(3), 873–904.
https://doi.org/10.1152/physrev.00041.2006

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PTSD and C-PTSD: Memory Scars of Stress

Posted on April 11, 2025 by rlannin1 / 0 Comment

Review of “Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways” by Johannes M. H. M. ReulThe article by Reul explains how the brain forms and stores memories of stressful events. It takes a deeper look into the molecular parts of this process. He outlines how exposure to stress activates signaling pathways (particularly through glucocorticoid hormones and noradrenaline) that lead to epigenetic modifications and gene transcription changes in neurons, especially within the hippocampus and amygdala. These biological shifts affect how memories are formed, consolidated, and retained, which then often leaves lasting marks on an individual’s mental health. Reul has an important point in his paper that stress memory formation is not simply a switch that turns on or off, but a complex process that varies depending on the intensity and duration of the stressor, as well as individual genetic and environmental factors [1].

The Biology Behind PTSD and C-PTSD: Stress Leaves a Mark

Stress is something we all know, to varying degrees. A traffic jam, a missed deadline, or a tense conversation are all moments that come and go. But what happens when stress doesn’t just pass? What happens when it affects the biology of our brains? This is the core of Post-Traumatic Stress Disorder (PTSD) and Complex PTSD (C-PTSD), where memories of trauma don’t fade, but persist. They are vivid, intrusive, and disruptive [2].

CPSTD vs PTSD: definitions, similarities and differences - Priory — See the similarities and differences between CPTSD and PTSD here.

This matters because millions of people globally live with PTSD or C-PTSD, often silently [3]. Veterans, survivors of abuse, refugees, and even those exposed to chronic stress in childhood or adulthood carry the weight of painful memories that persist. These aren’t just psychological burdens. They are deeply biological and rooted in how our brains process and encode trauma at a molecular level.

Understanding this is crucial, because trauma isn’t a rare event. It’s a public health issue at this point in society. The science behind stress memory formation, like the work detailed by Johannes Reul, reveals not only the how behind trauma memory, but also the why (why some people recover while others remain stuck) [1].

This understanding is far from complete. PTSD and C-PTSD can be difficult to treat. Traditional talk therapy and medication can help, but not for everyone. The brain’s response to traumatic stress is very nuanced, involving cascades of molecular signals, epigenetic changes, and structural shifts in brain areas like the amygdala and hippocampus. For people with C-PTSD (often linked to prolonged, repeated trauma like childhood abuse rather than PTSD’s acute event), the challenge can be much more complex. Their brains don’t just react to a single traumatic event; they adapt to a world in which trauma is the norm [2].

Memory is Key

But the core issue lies in memory: why are these traumatic memories so persistent? Why do they resurface without warning? Why are they embedded so deeply in the fabric of who we are?

The insights from Reul’s research outline the journey from stress exposure to lasting memory through molecular biology. He reveals potential intervention points. For instance, if we can modulate how stress hormones affect gene transcription right after a traumatic event, could we prevent PTSD from developing? Could future therapies target epigenetic markers to “soften” traumatic memories without erasing them entirely [1]?

This research doesn’t just decode how trauma shapes memory. It also looks at a possible course toward healing. It tells us that trauma is not just stored in the psyche, but also in the synapses, genes, and proteins that shape our brain’s response to the world [4].

The Mind and Soul Foundation : PTSD — Here we can see the difference in memory consolidation between a “normal” brain and a brain experiencing trauma.

Societal and Future Impact

So what does this mean for us, for society, for the future? It means rethinking trauma care as not just a psychological issue, but a neurobiological one. It means investing in early intervention, especially for children and communities exposed to chronic stress. It raises powerful questions: Can we “edit” traumatic memories without compromising identity? What ethical challenges arise from altering memory? Would we one day vaccinate against PTSD?

And here’s the takeaway: Trauma is not just remembered- it is encoded. Understanding the biology behind PTSD and C-PTSD allows us to move beyond stigma and into a future where treatment is personalized and preventative. If the brain can change in response to trauma, it can also change in response to care.

Let’s keep asking questions. How do we turn understanding into healing? And let’s stay curious, because the science of memory isn’t just about the past, it’s about shaping the future.

[1] Reul, J. M. H. M. (2014). Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways. Frontiers in Psychiatry, 5. https://doi.org/10.3389/fpsyt.2014.00005

[2] Danfeng Li, Jiaxian Luo, Xingru Yan, & Yiming Liang. (2023). Complex Posttraumatic Stress Disorder (CPTSD) as an Independent Diagnosis: Differences in Hedonic and Eudaimonic Well-Being between CPTSD and PTSD. Healthcare, 11(1188), 1188. https://doi.org/10.3390/healthcare11081188

[3] Guideline Development Panel for the Treatment of PTSD in Adults, American Psychological Association. (2019). Summary of the clinical practice guideline for the treatment of posttraumatic stress disorder (PTSD) in adults. The American Psychologist, 74(5), 596–607. https://doi.org/10.1037/amp0000473

[4] Herman, J. (2012). CPTSD is a distinct entity: comment on Resick et al. (2012). Journal of Traumatic Stress, 25(3), 256–7; discussion on 260–3. https://doi.org/10.1002/jts.21697

Community/Disease/Health/Hot topics

Stress: The Memory That Sticks

Posted on April 9, 2025 by Meg / 0 Comment

Original artstract by M. Shercliffe.

We’ve all experienced moments of intense stress that seem burned into our memories, whether it’s a near-miss car accident, a traumatic event, or even the anxiety of a final exam. But how does the brain cement these stressful experiences into long-term memory? The paper “Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways” [1] explores the molecular events behind this process, revealing a complex interaction between hormones, neurotransmitters, and epigenetic modifications.

Understanding the relationship between stress and memory formation begins with the hippocampus, a brain region critical for memory formation. When faced with psychological stress (like a rat being forced to swim in a lab tank, or a human speaking in front of a large crowd), the hippocampus becomes activated, in turn activating a cascade of molecular events that help encode the experience. Neurons firing in the hippocampus are not the only factor, glucocorticoids (stress hormones like cortisol in humans, or corticosterone in rats) play a significant part.

The paper highlights that these hormones don’t just passively float around, they actively shape how neurons respond to stress by interacting with glucocorticoid receptors (GRs). GRs act in combination with NMDA receptors, a glutamate receptor essential for learning and memory. Together, they trigger a signaling pathway involving ERK-MAPK, a series of proteins that relay stress signals into the nucleus of neurons.

Inside the nucleus, this stress-induced signaling leads to epigenetic modifications: chemical tags on DNA and its associated histones that regulate gene expression without altering the genetic code itself. Specifically, stress causes two key changes on histone H3, and is demonstrated in the psychological stress pathway in Figure 1 below:

Phosphorylation at serine 10 (S10)
Acetylation at lysine 14 (K14)

This dual mark, H3S10p-K14ac, acts like a molecular switch, opening up tightly wound DNA so that genes can be transcribed. Which genes get turned on? Immediate-early genes (IEGs), like c-Fos and Egr-1, are crucial for synaptic plasticity and memory consolidation[1].

Figure 1. Psychological stress-activated signaling pathways in the dentate gyrus granule neurons. Psychological stress activates the GR and NMDAR/ERK/MAPK pathways [1].

However, this epigenetic mechanism isn’t universal across the brain. While many regions activate c-Fos and Egr-1 during stress, only in the dentate gyrus (a subregion of the hippocampus) does their expression require H3S10p-K14ac[1]. This suggests that dentate gyrus neurons keep these genes inactivated under normal conditions, only releasing them when stress demands it.

What’s novel about this research is that it illustrates how glucocorticoids and glutamate signaling collaborate. Traditionally, steroid hormones like glucocorticoids were thought to act slowly, binding to receptors in the nucleus and modulating gene expression over hours. However, this research suggests that GRs physically interact with phosphorylated ERK to increase the activity of downstream kinases like MSK1 and Elk-1[1].

This interaction happens within minutes of stress, allowing glucocorticoids to amplify glutamate-driven signals and accelerate epigenetic modifications. Thus, GRs serve to amplify the ERK-MAPK pathway, ensuring the stressful memory is highly encoded.

Thankfully, the brain doesn’t let stress run unchecked. GABA, the brain’s primary inhibitory neurotransmitter, modulates the dentate gyrus’s response to stress through a baseline level of inhibition. This finding is supported by studies of drug interactions:

Anxiolytics (like lorazepam, a benzodiazepine) suppress stress-induced H3S10p-K14ac and c-Fos activation.
Axiogenics (like FG7142, a GABA-A receptor antagonist) do the opposite, increasing epigenetic and gene responses.

Even exercise plays a role. Long-term voluntary running in rats reduces anxiety-like behavior and dampens stress-induced ERK-MAPK signaling, likely by enhancing GABA synthesis[1]. This fits with real-world observations that exercise can help mitigate stress disorders[2].

Understanding these mechanisms has real implications for stress-related disorders like PTSD and anxiety. In vulnerable individuals, the balance between stress-induced memory formation and adaptive coping may go awry.

Hyperactive GR/ERK-MAPK signaling: This might lead to the over-consolidation of traumatic memories (e.g. PTSD flashbacks).
Dysregulated GABA control: Could result in excessive fear responses or failure to dampen stress reactions[1].

This also opens doors for potential therapies. If researchers can pinpoint drugs that target these epigenetic or signaling pathways (like MSK1 or Elk-1) there’s potential to disrupt maladaptive stress memories without affecting useful ones.

This research paints a vivid picture of how stress etches itself into our brains. It’s not just about neurons firing, it’s a combination of hormones, neurotransmitters, and epigenetic marks. While evolution likely designed this system to help us remember threats, sometimes it overshoots, leaving us stuck in loops of anxiety or trauma. The good news? The brain is extremely plastic. Exercise, therapy, and even pharmacological interventions can adjust these pathways, offering hope for better stress resilience.

Stressful events trigger glucocorticoids and glutamate signaling in the hippocampus, but the formation of long-term memories requires a precise epigenetic switch (H3S10p-K14ac) that activates memory-related genes. Therefore, understanding this mechanism reveals potential therapeutic targets for stress-related disorders like PTSD and anxiety.

References

[1] J. M. H. M. Reul, “Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways,” Front. Psychiatry, vol. 5, p. 5, Jan. 2014, doi: 10.3389/fpsyt.2014.00005.

[2] H. Alizadeh Pahlavani, “Possible role of exercise therapy on depression: Effector neurotransmitters as key players,” Behav. Brain Res., vol. 459, p. 114791, Feb. 2024, doi: 10.1016/j.bbr.2023.114791.

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Stress Leaves a Mark – Literally: Why the Way We Remember Trauma Matters

Posted on April 9, 2025 by ealslebe / 0 Comment

We all experience stress. And we all remember those moments when life seemed overwhelming—finals week, heartbreak, a fender bender, or worse. These memories shape how we see the world and how we respond to future challenges. But have you ever wondered why some stressful experiences stay with us for years, while others fade quickly? Or why some people develop anxiety disorders or PTSD after trauma, while others don’t? Therefore, it’s essential that we understand not just that we remember stress—but how our brain encodes it, right down to the molecular level.

The Science of Stressful Memories: A Look Inside the Brain

In the article Making Memories of Stressful Events by Dr. Johannes Reul, a remarkable discovery is unpacked: when we undergo psychological stress, our brain physically changes to record that experience—starting with our DNA.

Here’s how it works: stress triggers the release of glucocorticoid hormones (like cortisol), which bind to glucocorticoid receptors (GRs) in the brain—especially in the hippocampus, the region responsible for memory. At the same time, glutamate activates NMDA receptors, kicking off a signaling cascade called the ERK-MAPK pathway. [1]

The magic happens when these two systems converge, forming a biological memory-making machine. This convergence leads to changes in the structure of histones, the proteins that package DNA. Specifically, a dual histone mark (H3S10 phosphorylation and K14 acetylation) appears, unlocking genes like c-Fos and Egr-1 which are crucial for memory consolidation. [1]

Why Should You Care

This research explains why some people develop disorders like PTSD after trauma—and others don’t. Only about 10–20% of people develop lasting mental health issues after a major stressor. This suggests that the way our brains process stress at the molecular level plays a major role in our mental resilience. [2]

Figure 1 [3]: Showing the difference between GABA in a normal functioning adult under non-stressful conditions and one under stressful conditions.

The study also revealed that GABA, the brain’s calming neurotransmitter, modulates this memory-encoding process (see Figure 1). More anxious individuals have lower GABAergic tone, which means their brains are more reactive to stress, forming stronger stress memories. Conversely, exercise was shown to increase GABA and reduce the brain’s stress response. [1]

So if you’ve ever wondered whether daily exercise can really help manage anxiety—the answer is, yes, even at the level of your DNA.

What Should You Take Away From This

This isn’t just a neuroscience geek-out—it’s a story about how our bodies remember, and how we can influence those memories.

If you’re a student, knowing that high anxiety makes stressful moments “stick” more might encourage you to seek out mental wellness tools before finals week (Figure 2).

If you’re managing anxiety, exercise isn’t just about physical health—it’s an epigenetic intervention.

Figure 2 [4]: Wellness tools that can help relieve stress.

And if you’re someone who’s endured trauma, this science brings hope. Understanding the pathways that encode stress memories means we are one step closer to therapies that can help “unwrite” them.

Let’s Reframe the Conversation

Instead of viewing stress as something abstract or purely emotional, we can now see it as a physical imprint (Figure 3), a story our neurons etch into our DNA. And that story is shaped by biology, yes—but also by environment, habits, and resilience.

Understanding this empowers us to care for our mental health not just with willpower, but with scientific insight.

So the next time someone tells you that stress is “all in your head”—you can smile and say, “Yes, and it’s in my chromatin too.”

Figure 3 [5]: Each story shapes our biology into the person we are today.

References

[1] Reul J. M. (2014). Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways. Frontiers in psychiatry, 5, 5. https://doi.org/10.3389/fpsyt.2014.00005

[2] Schneiderman, N., Ironson, G., & Siegel, S. D. (2005). Stress and health: psychological, behavioral, and biological determinants. Annual review of clinical psychology, 1, 607–628. https://doi.org/10.1146/annurev.clinpsy.1.102803.144141

[3] Mody, I., & Maguire, J. (2012). The reciprocal regulation of stress hormones and Gabaa receptors. Frontiers in Cellular Neuroscience, 6. https://doi.org/10.3389/fncel.2012.00004

[4] Rebecca Valdez, M. (2024, June 10). Techniques to reduce stress and anxiety. Verywell Health. https://www.verywellhealth.com/how-to-reduce-stress-5207327

[5] Brain+puzzles images – browse 163,431 stock photos, vectors, and video. Adobe Stock. (n.d.). https://stock.adobe.com/search?k=brain%2Bpuzzles

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I Can Only Stress the Importance

Posted on April 9, 2025 by rhurley1 / 0 Comment

The article we have covered in a previous week, “Making Memories of Stressful Events: a journey along epigenetic, gene transcription, and signaling pathways” by Johannes M. H. M. Reul was an article about stressful events having a long lasting impact on both behavior and memories. Basically, we know already that memories are a feature of having a brain. However, due to this feature, between ten to twenty percent of human beings has developed some kind of stress disorder because of at least one traumatic events.The topic today is why people should care about this topic and what the people must know, so without further ado let’s get reading!

The article informs us of an experiment where they took lab mice through an experience where they put the mice in an enclosure which they flooded. Though, the article specifically focuses mainly on reactions between the initial and repeated attempts at this where the mice eventually began to connect the pieces together and began floating naturally. As a result of this connection, we can now classify here that traumatic moments can very much form memories.

Figure one, pictured above, from the article mentioned above is especially excellent at explaining this where it was needed (excellently timed, or in other words placed well). That piece is a bar chart expressing the response of these lab rats upon getting forced to swim for long periods of time. Although, one slight problem could be that it could feel a large bunch overwhelming if you’re not too familiar with the applied terms of figure one in the Neuroscience field. This was an excellent piece to me for it is maximized simplicity because, for clear reasons, that kind of thing strongly helps. The figure may also benefit people uninvolved in Neuroscience as well because figure one uses so much brief, yet descriptive, labeling, and I find that effective myself in general because it’s easy on the eyes to track or logicate.

Now, at this point, one, such as yourself, may wonder why people really should care about all the above information. Well, let’s answer with essential basics to answer ourselves by quickly asking ourselves something simpler first; what really is an anxiety disorder? Well, the answer is absolutely nothing short of a true tragedy. According to Cleveland Clinic, an anxiety disorder is known as “a group of mental health conditions that cause fear, dread and other symptoms that are out of proportion to the situation” (Cleveland Clinic 2025). Considering that we know about these symptoms as a consequence, it’s no shock to pretty much anyone that such a scenario can turn serious fast. Let us put this into perspective with another topic.

In my class, I personally examined the various animal model types used in studies of stress. Surprisingly, I learned from authors at Science Direct of various vertebrate animals, such as animals we often think of as pets (pigs, dogs, rabbits, and so on) used to model the effects stressful events have on the heart muscle (Nicola Maggio and Menahem Segal, 2019). It is nothing short of incredible that we have the option to use inhuman specimens to reduce the need for real human beings in experiments that would be way too dangerous for us all, but I insist that we must subscribe to love and ethics when we do so.

Works Cited:
1) “Making Memories of Stressful Events: a journey along epigenetic, gene transcription, and signaling pathways” by Johannes M. H. M. Reul

2) Cleveland Clinic 2025 on anxiety disorders

3) “Stress, Corticosterone, and Hippocampal Plasticity” by Nicola Maggio and Menahem Segal, 2019

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Trauma’s Code: Stress Signals and the Epigenetic Blueprint

Posted on April 9, 2025 by jcopiske / 0 Comment

Trauma’s Code: Stress Signals and The Epigenetic Blueprint

Stress is a universal human experience, yet its impact on the brain often goes unnoticed. It leaves a lasting molecular and cellular footprint, shaping emotions, behaviors, and memories. By unraveling the science behind stress responses, we can better understand how stress rewires the brain and explore the critical roles of neurotransmitters and epigenetic changes in trauma recovery.

Understanding PTSD, Anxiety, and Stress

Anxiety and stress disorders are widely prevalent among individuals with PTSD, producing emotional and physiological responses that affect overall well-being. The interactions between stress and emotional or cognitive processing can reveal how such mechanisms contribute to the development and persistence of PTSD and stress.

The process of converting DNA instructions into RNA is fundamental for driving cellular responses; in this case of stress, glucocorticoid hormones are involved, which play a pivotal role in regulating the brain’s stress response and the functionality of the hippocampus, which is a region essential for memory and emotional regulation.

GABAergic neurons are crucial, which regulate brain excitability, and the limbic brain structures, including the amygdala and hippocampus, as the emotional core of the brain.

Finally, the role of vital signaling pathways, such as ERK-MAPK, and transcription factors like CREB, emerges as essential contributors to the molecular changes induced by stress. As shown in Fig.2.

What is an Epigenetic Pathway?

Epigenetic pathways are powerful mechanisms that regulate how stress impacts the brain, without altering the underlying DNA sequence. These processes involve modifications to histones, which are proteins that DNA wraps around. As well as chemical additions like methylation or acetylation, which influence whether specific genes are “switched on” or “off.”

In the context of stress and PTSD, epigenetic changes can increase or suppress gene expression, particularly in areas like the hippocampus and amygdala. For example, stress-induced histone modifications, shown in Fig. 3 such as serine10 phosphorylation and lysine14 acetylation, play a role in activating immediate early genes (IEGs) critical for neural adaptation and behavioral responses. [4]

These epigenetic marks have effects across signaling pathways like ERK-MAPK, reshaping how the brain responds to fear and anxiety over time. Such changes can be enduring, encoding trauma and contributing to long-term vulnerability to PTSD, The dynamics between stress and the epigenetic marks emphasize the brain’s remarkable adaptability and synaptic plasticity. [5]

Acute Stress vs Chronic Stress

Acute stress can sometimes be beneficial, as it primes the brain for quick responses. However, chronic stress is a significant risk factor for anxiety disorders.
Chronic stress or PTSD induce changes in the amygdala, PFC, and hippocampus which contribute to heightened anxiety, impaired emotional regulation, and difficulty distinguishing between real and perceived threats.

Acute Stress

Acute stress is short-term and typically arises in response to immediate threats or challenges, such as a sudden deadline or a near-miss car accident.

The brain’s amygdala detects the threat and signals the hypothalamus, which activates the sympathetic nervous system. This triggers the “fight-or-flight” response, releasing stress hormones like adrenaline and cortisol.

Effects on the Brain:

Enhancement of glutamate release in the PFC, improving focus and decision-making temporarily.
Activates the hippocampus, aiding memory formation related to the stressful event.
Once the stressor is resolved, the parasympathetic nervous system restores balance, reducing cortisol levels.[1]

Chronic Stress

Chronic stress occurs when stressors persist over time, such as ongoing financial difficulties or a toxic work environment.

This causes prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis , which then leads to sustained cortisol release.

Affects on the Brain

Hippocampus: Chronic cortisol exposure can cause atrophy of hippocampal neurons, impairing memory and learning. Chronic cortisol causes dendritic shrinkage and spine loss, impairing episodic memory and spatial navigation.
Prefrontal Cortex: Reduced activity in the PFC weakens decision-making and emotional regulation. Dendrites in the medial PFC retract, impairing memory and emotional resilience, while the orbitofrontal cortex (OFC) shows dendritic expansion associated with hypervigilance.
Amygdala: Becomes hyperactive, heightening fear and anxiety responses. Acute stress increases dendritic growth temporarily, but chronic stress leads to more enduring expansions in basolateral amygdala (BLA) dendrites, heightening anxiety and fear responses.
Neuroplasticity: Chronic stress disrupts synaptic plasticity, leading to long-term changes in brain circuits associated with anxiety and depression. [2]

Acute Stress	Chronic Stress
Short-term HPA axis activation.	Prolonged HPA axis activation and dysregulation.
Boosts PFC activity for focused thinking.	Impairs PFC function, weakening decision-making and emotional regulation.
Enhances hippocampal memory encoding.	Causes hippocampal atrophy and reduced neurogenesis.
Balanced glutamate levels support plasticity.	Excess glutamate triggers excitotoxicity.
Parasympathetic system restores balance.	Persistent cortisol alters brain circuits.

Stress and Structural Changes in The Brain

Anxiety and stress disorders are common among individuals with PTSD, producing emotional and physiological responses that can affect overall well-being. Critical aspects include gene transcription, the process of converting DNA instructions into RNA to drive cellular responses, and the role of glucocorticoid hormones, which influence the brain’s ability to respond to stress. The adrenal cortex produces corticosterone, which is a vital glucocorticoid hormone involved in the body’s stress response. As shown in Fig. 5

Corticosterone plays a central role in regulating metabolism, immune response, and the HPA axis. When the body encounters stress, the adrenal cortex releases corticosterone into the bloodstream to help maintain homeostasis. This hormone influences the energy balance by increasing glucose availability, ensuring that the body has enough resources to respond to the stressor.

Additionally, the hippocampus, is highlighted alongside GABAergic neurons that manage brain excitability through the inhibitory neurotransmitter GABA. Furthermore, limbic brain structures such as the amygdala and hippocampus, as well as critical signaling pathways like ERK-MAPK and transcription factors such as CREB, play a significant role in the stress-induced molecular changes.

Neurotransmitters Involved in Stress

Glutamate: As the brain’s primary excitatory neurotransmitter, glutamate enables rapid communication between neurons. Acute stress uses glutamate effectively to enhance cognitive performance, but chronic stress floods the brain, causing excitotoxicity and disrupting synaptic plasticity. Glutamate is critical for associative learning and emotional processing under stress. Dysregulated glutamate signaling contributes to distortions in how PTSD patients process information. [3]
GABA (Gamma-Aminobutyric Acid): The brain’s primary inhibitory neurotransmitter, GABA helps counterbalance glutamate’s excitatory effects, calming hyperactive neurons. Chronic stress reduces GABA function, heightening anxiety and emotional reactivity.
Dopamine: Acute stress briefly boosts dopamine, aiding motivation and focus. Chronic stress depletes dopamine, contributing to loss of pleasure and depression.
Serotonin: Regulates mood and emotional processing. Stress can diminish serotonin levels, increasing vulnerability to anxiety and depression.
Noradrenaline (Norepinephrine): Heightens alertness and attention during acute stress but can lead to heightened vigilance and overreaction under chronic stress.

These neurotransmitters form the biochemical foundation for how the brain processes and adapts to stress, playing a critical role in shaping behaviors and emotional outcomes in PTSD. As seen in Fig. 6 Optimal conditions versus stressful conditions in a neurotransmitter.

Why This Matters

Stress and PTSD leave lasting imprints on the brain, from changes in neurotransmitter function to epigenetic marks that shape how we process fear, memory, and resilience. We can understand the brain’s plasticity allows it to adapt to stress, but also how chronic stress can disrupt this balance, leading to vulnerabilities like anxiety, depression, and PTSD.

Understanding the molecular and cellular effects of stress gives us more than knowledge, it gives the potential future of treatment. By targeting pathways like ERK-MAPK or leveraging therapeutic potential in neurotransmitters such as GABA and glutamate, science paves the way for innovative treatments that go beyond symptom management to address the root causes of trauma.

REFRENCES

Gudsnuk, K., & Champagne, F. A. (2012). Epigenetic influence of stress and the social environment. ILAR journal, 53(3-4), 279–288. https://doi.org/10.1093/ilar.53.3-4.279

Howie, H., Rijal, C. M., & Ressler, K. J. (2019). A review of epigenetic contributions  to post-traumatic stress disorder . Dialogues in clinical neuroscience, 21(4), 417–428. https://doi.org/10.31887/DCNS.2019.21.4/kressler

JM;, R. (n.d.). Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways. Frontiers in psychiatry. https://pubmed.ncbi.nlm.nih.gov/24478733/

Martin, E. I., Ressler, K. J., Binder, E., & Nemeroff, C. B. (2009). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. The Psychiatric clinics of North America, 32(3), 549–575. https://doi.org/10.1016/j.psc.2009.05.004

FOOTNOTES

[1] JM;, R. (n.d.). Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways. Frontiers in psychiatry. https://pubmed.ncbi.nlm.nih.gov/24478733/

[2] JM;, R. (n.d.). Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways. Frontiers in psychiatry. https://pubmed.ncbi.nlm.nih.gov/24478733/

[3] Martin, E. I., Ressler, K. J., Binder, E., & Nemeroff, C. B. (2009). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. The Psychiatric clinics of North America, 32(3), 549–575. https://doi.org/10.1016/j.psc.2009.05.004

[4] Howie, H., Rijal, C. M., & Ressler, K. J. (2019). A review of epigenetic contributions  to post-traumatic stress disorder . Dialogues in clinical neuroscience, 21(4), 417–428. https://doi.org/10.31887/DCNS.2019.21.4/kressler

[5] Gudsnuk, K., & Champagne, F. A. (2012). Epigenetic influence of stress and the social environment. ILAR journal, 53(3-4), 279–288. https://doi.org/10.1093/ilar.53.3-4.279

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The Stress-Memory Puzzle: Why Studying the Human Brain Isn’t So Simple

Posted on April 8, 2025 by Nessa Angau / 0 Comment

Stress Enhances Some Memories—but Not Always

It’s well-known that stressful events are often remembered more vividly than neutral ones. From an evolutionary standpoint, this makes sense: remembering where the lion chased you could save your life. But the biology behind this is anything but simple.

Reul (2014) explains that strong psychological stressors initiate a cascade of molecular changes in the hippocampus and amygdala, key regions involved in learning, memory, and emotion. In animal studies, stress-related memory formation relies heavily on glucocorticoid hormones like cortisol (or corticosterone in rodents), which are released during stress and bind to glucocorticoid receptors (GRs) in neurons [1].

Simulating Stress in a Lab is Tricky

In animal studies, stress can be induced through tests like the forced swim test or Morris water maze, which reliably elevate glucocorticoids and activate memory formation pathways. But in humans, ethically inducing high levels of stress is much harder—researchers can’t just dunk people in cold water or give them electric shocks.

This means that lab-based stress tests (like giving a surprise math quiz or asking participants to speak in front of a crowd) often fall short of triggering the deep biological mechanisms that actual trauma or survival-related stress would.

Not Everyone Reacts to Stress the Same Way

One of the biggest obstacles is individual variability. Some people under stress develop strong, clear memories. Others forget details or block the event entirely. This is partly explained by variations in anxiety levels and GABAergic control, as Reul’s study highlights [1].

In the hippocampus, a person’s anxiety level influences how their neurons respond to stress at the molecular level. Higher anxiety tends to amplify stress responses—via both hormone release and epigenetic changes—making certain memories stronger or more “sticky” [2].

Epigenetics: The Memory Code That Keeps Changing

MAPK Erk pathway - Cusabio — Figure 1. As shown in this figure is the MAPK-ERK Signaling Pathway [3].

Stress doesn’t just flip a switch in your brain; it rewires it—literally. Reul and colleagues found that stress activates the ERK-MAPK signaling pathway, which leads to a specific modification on histone proteins: H3S10 phosphorylation and K14 acetylation (H3S10p-K14ac). This chromatin remodeling opens up DNA for transcription of “immediate-early genes” like c-Fos and Egr-1, which are critical for long-term memory consolidation.

But this change doesn’t happen uniformly across the brain. These epigenetic marks are highly specific to areas like the dentate gyrus in the hippocampus, and are influenced by prior experiences, local interneuron activity (especially GABAergic tone), and afferent input from emotional centers like the amygdala [4].

We Still Don’t Know the Full Picture

Despite decades of research, we still can’t fully predict who will remember a traumatic event clearly, who will develop PTSD, and who will walk away largely unscathed. Reul’s research shows that the consolidation of stress-related memories depends on an intricate interaction between hormones, neurotransmitters, genetics, and environmental context.

The bottom line? Studying stress and memory is hard because the human brain is built for complexity. It’s not just about remembering what happened—it’s about how your biology, mood, history, and genes all converge in that moment.

And in the end, understanding that convergence might just be the key to treating stress-related disorders like PTSD and anxiety.

Resources

[1] Reul, J. M. H. M. (2014). Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways. Frontiers in Psychiatry, 5, Article 5. https://doi.org/10.3389/fpsyt.2014.00005

[2] Robinson, O. J., Vytal, K., Cornwell, B. R., & Grillon, C. (2013b). The impact of anxiety upon cognition: Perspectives from human threat of shock studies. Frontiers in Human Neuroscience, 7(203). https://doi.org/10.3389/fnhum.2013.00203

[3] MAPK Erk pathway – Cusabio. (n.d.). Retrieved from www.cusabio.com website: https://www.cusabio.com/pathway/MAPK-Erk-pathway.html

[4] Kandler, C. (2021, June 22). Epigenetic Regulation – an overview | ScienceDirect Topics. Retrieved from www.sciencedirect.com website: https://www.sciencedirect.com/topics/psychology/epigenetic-regulation