Cobbers on the Brain – Page 6 – Student Commentary on the Neurological Sciences

Alzheimer’s and Insulin: Is Alzheimer’s Disease a “Type 3 Diabetes”?

Posted on February 19, 2025 by ealslebe / 0 Comment

Did you know that Alzheimer’s disease (AD) might have more in common with diabetes than we ever imagined? Scientists have discovered a powerful link between insulin resistance – the same problem at the heart of Type 2 Diabetes – and the brain changes seen in Alzheimer’s. Some even call AD “Type 3 Diabetes” because of how insulin dysfunction contributes to memory loss and cognitive decline. But how does this work? And could diabetes medications help fight Alzheimers? [1]

1,900+ Man Measuring Blood Sugar Stock Photos, Pictures & Royalty-Free Images - iStock

Figure 1 [2]

Insulin: More Than Just a Blood Sugar Regulator

We usually think of insulin as the hormone that controls blood sugar, but it also plays a vital role in the brain. Insulin helps neurons communicate, protects them from damage, and keeps brain cells energized. When everything is working well, insulin binds to receptors on brain cells, triggering pathways that support learning and memory.

Frontiers | Insulin Resistance in Alzheimer's Disease

Figure 2 [3]

But when insulin signaling is disrupted – known as brain insulin resistance – neurons can’t absorb glucose efficiently, leading to energy shortages, inflammation, and cell damage. This makes it harder for the brain to function, setting the stage for Alzheimer’s. [4]

The Early Warning Signs: Insulin Resistance in the Brain

Long before severe memory loss kicks in, brain insulin resistance begins to take hold – especially in areas critical for memory, like the hippocampus and cortex. Here’s what happens:

Neurons stop responding to insulin: Key signaling pathways that keep brain cells alive and functioning begin to break down.
Glucose metabolism slows down: Brain scans show that memory-related areas start using less glucose, making it harder to form new memories.
Inflammation and oxidative stress rise: Harmful molecules like TNF-a and IL-6 flood the brain, damaging neurons and worsening insulin resistance.

Adding to the problem, amyloid-beta oligomers – toxic protein clumps linked to AD – can actually cause insulin resistance in neurons. This creates a vicious cycle: insulin dysfunction fuels Alzheimer’s, and Alzheimer’s worsens insulin resistance. [5]

Insulin and Alzheimer's disease – Cobbers on the Brain

Figure 3 [6]

As Alzheimer’s Progresses: Insulin Dysfunction Gets Worse

As the disease advances, insulin resistance in the brain becomes severe:

Insulin receptors break down: The brain can’t properly respond to insulin, leading to widespread metabolic failure.
Neurons lose their survival signals: Key pathways, like P13K/Akt, that protect against cell death become disrupted.
Brain cells starve: Glucose metabolism crashes, leaving neurons without the energy they need to survive.
Amyloid plaques and tau tangles grow: These toxic proteins further block insulin signaling, accelerating brain cell death. [7]

Diabetes and Alzheimer’s: A Dangerous Connection

People with Type 2 Diabetes Mellitus (T2DM) are at a higher risk of developing Alzheimer’s – likely because both conditions involve insulin resistance and chronic inflammation. Research suggests that high insulin levels in the body can actually reduce insulin transport into the brain, making the problem worse.

Are Heat Shock Proteins an Important Link between Type 2 Diabetes and Alzheimer Disease?

Figure 4 [8]

Can Diabetes Drugs Help Treat Alzheimer’s?

Metformin: A common diabetes drug that may improve insulin sensitivity and reduce tau protein buildup in the brain.
Intranasal Insulin: Direct delivery of insulin to the brain (through the nose) has shown improvements in memory and cognitive function.
GLP-1 Receptor Agonists (e.g., Exenatide): These diabetes medications enhance insulin signaling and have anti-inflammatory effect in the brain.
Thiazolidinediones (e.g., Pioglitazone): These drugs improve insulin sensitivity and may reduce amyloid plaque formation.

Final Thoughts: What Can You Do?

While research on insulin-based Alzheimer’s treatments is ongoing, one thing is clear: managing blood sugar and insulin levels is crucial for brain health.

Here are some lifestyle tips to help reduce your risk:

Eat a balanced diet rich in Whole Foods, healthy fats, and fiber.
Exercise regularly to improve insulin sensitivity.
Get quality sleep – poor sleep can worsen insulin resistance.
Manage stress, as chronic stress affects insulin function.

Embrace Healthy lifestyle, take balanced diet, exercise, sleep, stress relief, no smoking 46149206 Vector Art at Vecteezy

Figure 5 [9]

Alzheimer’s disease is still a mystery in many ways, but understanding the insulin connection opens up new treatment possibilities. As science continues to evolve, one thing remains certain: taking care of your metabolic health is one of the best things you can do for your brain!

References

[1] de la Monte, S. M., & Wands, J. R. (2008). Alzheimer’s disease is type 3 diabetes—evidence reviewed. Journal of Diabetes Science and Technology, 2(6), 1101–1113. https://doi.org/10.1177/193229680800200619

[2] Man measuring blood sugar pictures, images and stock photos. iStock. (n.d.). https://www.istockphoto.com/photos/man-measuring-blood-sugar

[3] Ferreira, L. S. S., Fernandes, C. S., Vieira, M. N. N., & De Felice, F. G. (2018, October 23). Insulin resistance in alzheimer’s disease. Frontiers. https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00830/full

[4]Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and alzheimer’s disease. Neurochemistry International, 135, 104707. https://doi.org/10.1016/j.neuint.2020.104707

[5] Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., Holtzman, D. M., & Nathan, D. M. (2018). Brain insulin resistance in type 2 diabetes and alzheimer disease: Concepts and conundrums. Nature Reviews Neurology, 14(3), 168–181. https://doi.org/10.1038/nrneurol.2017.185

[6] Zimy. (2024, April 2). Insulin and alzheimer’s disease. Cobbers on the Brain. https://blog.cord.edu/cobbersonthebrain/2024/04/02/insulin-and-alzheimers-disease/

[7] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and alzheimer’s disease. Neurochemistry International, 135, 104707. https://doi.org/10.1016/j.neuint.2020.104707

[8] Movassat, J., Delangre, E., Liu, J., Gu, Y., & Janel, N. (2019, June 3). Hypothesis and theory: Circulating alzheimer’s-related biomarkers in type 2 diabetes. insight from the goto-kakizaki rat. Frontiers. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00649/full

[9] Sarkar, N. (n.d.). Embrace healthy lifestyle, take balanced diet, exercise, sleep, stress relief, no smoking. Vecteezy. https://www.vecteezy.com/vector-art/46149206-embrace-healthy-lifestyle-take-balanced-diet-exercise-sleep-stress-relief-no-smoking

Disease/Uncategorized

P13K and Alzheimers disease: The Domino Effect

Posted on February 19, 2025 by jcopiske / 0 Comment

The Domino Effect: Alzheimer’s disease follows a pathogenesis that includes a cascade of inflammation, synaptic dysfunction, and hyper-phosphorylation of Tau proteins. P13k is a serine/threonine protein kinase. This is an essential signaling component, especially in an irreversible neurodegenerative disease like Alzheimer’s.

(STK) serine/threonine kinase is responsible for cellular processing; within P13k, there is a catalytic subunit and a regulatory subunit. I like to think of the two as a relationship, similar to an employee and a manager. The catalytic subunit is an active site for phosphorylation and, in turn, enzymatically catalyzes a reaction. As the catalytic subunit responds to the regulatory subunit, the manager, its job is to facilitate, control, or inhibit these reactions.

P13K: The Trigger

P13K is an enzyme that grows cells and initiates cell communication by transmitting signals. It is a critical for synaptic health.
As P13k’s job is regulation, it can become uncontrolled or abnormal and, in turn, the body responds in vicious ways as the P13k pathway is principle in human disease
The P13k/Akt pathway combustion accelerates neurodegeneration which triggers this cascade of events.

Akt Activation

Akt activation is triggered by various cellular components involved in Alzheimer’s disease, stems primarily from Amyloid–B and Neurofibrillary tangles, which are neurodegenerative proteins found in patients with Alzheimer’s.
The activation of PI3K facilitates Akt.
Serine/Threonine protein has a catalytic domain and a regulatory domain, involved in PI3K/Akt pathways and phosphoinositide.
Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for the phosphorylation of Akt, which has three subtypes: Akt1, Akt2, and Akt3.

Phosphorylation of GSk-3B

Akt phosphorylates Glycogen Synthase Kinase-3B (GSK-3B).
GSk-3B propagates apoptotic signals and facilitates degradation.
This, however, creates inactivation of GSk-3B.. which in turn accelerates Tau protein phosphorylation.

Tau Proteins

Tau proteins are the main component of neurofibrillary tangles, which is the abnormal protein that promotes Alzheimer’s disease.
Inactivation of GSK-3B causes the hyper-phosphorylation of Tau proteins.
The hyper-phosphorylation of Tau proteins drives disease development.
Tau proteins are essentially responsible for axonal transport and neurite growth, so when Tau becomes hyper-phosphorylated ,it cannot attach regularly to microtubules.
Therefore, neurofibrillary tangles are formed, which affect cell communication and plasticity between neurons.

1-s2.0-S1355814523002419-Fig2_HTML_lrg.jpg (2030×988) — Figure1: Comparing P13K pathway in normal functioning via P13k in Alzheimers Disease

Alzheimers disease & P13K

P13K Pathway is critical in a signaling cascade which develops apoptosis and neurodegeneration,
Creates extracellular Amyloid- B plaques which are formed by amyloid cursor protein
Creates intracellular neurofibrillary tangles occurring from hyper-phosphorylated Tau proteins.
Amyloid-B and Neurofibrillary tangles are pathological marks that indicate Alzheimers disease.
In relation to therapeutic research, insulin signaling has been used as a neuromodulator to create ‘brain insulin resistance.’ which stemmed from the idea that dysfunctional insulin signaling was contributing to the symptomatology of Alzheimer’s disease.
Dementia is a pathological disease, as Alzheimer’s follows the P13k/Akt pathway it produces hallmarks of AD, therefore, generates dysregulated brain insulin signaling.

Footnotes:

Povala, G., Bastiani, M. A. D., Bellaver, B., Ferreira, P. C. L., Ferrari-Souza, J. P., Lussier, F. Z., Souza, D. O., Rosa-Neto, P., Zatt, B., Pascoal, T. A., Zimmer, E. R., & Initiative, the A. D. N. (2022, January 1). Serine/threonine kinase activity associates with brain glucose metabolism changes in alzheimer’s disease. medRxiv. https://www.medrxiv.org/content/10.1101/2022.10.31.22281751v1.full

Razani, E., Pourbagheri-Sigaroodi, A., Safaroghli-Azar, A., Zoghi, A., Shanaki-Bavarsad, M., & Bashash, D. (2021, November). The PI3K/akt signaling axis in alzheimer’s disease: A valuable target to stimulate or suppress? Cell stress & chaperones. https://pmc.ncbi.nlm.nih.gov/articles/PMC8578535/

Rosenberger, A. F. N., Hilhorst, R., Coart, E., García Barrado, L., Naji, F., Rozemuller, A. J. M., van der Flier, W. M., Scheltens, P., Hoozemans, J. J. M., & van der Vies, S. M. (2016). Protein kinase activity decreases with higher braak stages of alzheimer’s disease pathology. Journal of Alzheimer’s disease : JAD. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927853/

SP;, A. A. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and alzheimer’s disease. Neurochemistry international. https://pubmed.ncbi.nlm.nih.gov/32092326/

Taylor, H. B. C., & Jeans, A. F. (2021, August 31). Long-term depression links amyloid-β to the pathological hyperphosphorylation of tau. Cell Reports. https://www.sciencedirect.com/science/article/pii/S2211124721010810

Disease/Health

Concussions are Bad, you see

Posted on February 19, 2025 by rhurley1 / 0 Comment

The article we have covered in a previous week, “The New Neurometabolic Cascade of Concussion” by Christopher Giza and David Hovea was an article about the various neurological aspects of the traumatic impacts of a concussion. Basically, it works as following; we know from even our introductory Neuroscience classes that the brain can be a very delicate organ full of life and power due to the beyond constant action potentials. However, must that process fail, such as damages interrupting this process along the way, various things can go wrong to cause a tragic concussion.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 that some of the distinguishable characteristics of a concussion are connected to both trauma and neurodegeneration. Though, the article specifically focuses mainly on damages. As a result of this connection, we can now classify concussions as a dangerous emergency scenario worthy of calling the infamous 911/999 number upon encounter.

Figure two from the article mentioned above is specifically excellent at explaining the despairing severity of a concussion at a cellular level where it was needed (excellently timed, or in other words placed well). That piece is simultaneously even a diagram which shows what goes wrong with a concussion at the micro-scale which were broken neurons leading to leakage of essential components (neurotransmitters, energy, potassium, calcium, and more)^1. Although, it could feel a tad bit overwhelming if you’re not too familiar with the applied terms of figure two 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 two works similarly like speech bubbles in comic books with all the 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 a concussion? Well, concussion is not very nice at all and looks even worse when examined scientifically. According to Mayo Clinic, a concussion is defined as a, “mild traumatic brain injury that affects brain function….”^2 Considering that we know the brain to be the most vital organ of all in the body, it’s no shock that such a scenario is serious and even severe. This reminds me of something.

This human body response to direct brain trauma, a concussion, reminds me of my own concept of “alternative neurology.” Alternative neurology is a concept I have conceptualized in class just a couple weeks ago. Alternative neurology is the term, or in other words an unofficial term, for the brain’s ability to adapt to form after damages forces cell death and other happenstances. My term may sound much like neuroplasticity, a word used to reference the brain’s ability to adapt to stimulus in general, but rather alternative neurology adaptation refers to so-called “bad stimulus” solely whereas neuroplasticity includes any stimulus at all.

Footnotes Citation:

1) “The New Neurometabolic Cascade of Concussion” by Christopher Giza and David Hovea.
2) https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594

Uncategorized

New Frontiers in Alzheimer’s Treatment: Exploring More Approaches

Posted on February 19, 2025 by rlannin1 / 0 Comment

Introduction

Today’s topic is the treatment for Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative disorder that impacts memory, thinking, and behavior. It often leads to a progressive decline in all cognitive functions. Alzheimer’s disease is one of the most pressing health challenges facing aging populations today, no matter where in the world. With millions diagnosed, finding effective treatments is crucial not only for improving the quality of life for those diagnosed but also for easing the burden on caregivers, healthcare systems, and society as a whole.

This image shows the degradation of the brain when affected with Alzheimer's disease. — This image shows the degradation of the brain when affected with Alzheimer’s disease.

The search for Alzheimer’s treatments is connected to larger issues like the aging population, ethics of medical interventions, and healthcare resources. As life expectancy increases, Alzheimer’s disease is becoming more common. We need to make advancements in treatment for societal well-being. The ongoing research into Alzheimer’s connects to areas of neuroscience, biotechnology, and personalized medicine. Scientists are working to expand the boundaries of what we know about the brain and how diseases can be treated.

Treatments

Alzheimer’s disease treatments focus on managing symptoms and slowing progression. There is no cure. Medications like cholinesterase inhibitors (for example, Donepezil) and glutamate regulators (ex. Memantine) can help improve memory and cognitive function [1]. Newer treatments like monoclonal antibodies (ex. Aduhelm and Leqembi) target amyloid plaques specifically in the brain, stopping their growth [2]. Insulin treatments for Alzheimer’s, such as intranasal insulin, are being explored because insulin resistance in the brain contributes to cognitive decline, just like how insulin resistance in the body is a big factor in Type 2 diabetes. These treatments aim to enhance memory and cognitive function similarly to how insulin therapy helps manage glucose levels in diabetes. Lastly, GLP-1 agonists, like Ozempic, show possible promise for protecting brain cells and improving cognition [3]. Outside of medication, lifestyle changes like exercise, a healthy diet, and cognitive therapies can support brain health and well-being.

These findings note the challenge of Alzheimer’s disease. We are in need of finding treatments that can not only stop the degradation of the brain, but heal what damage has been done [4]. Exploring insulin therapies and GLP-1 agonists (like Ozempic) is causing researchers to shift focus to the brain’s metabolic processes, which may open up new avenues for slowing cognitive decline and improving quality of life for patients. These treatments provide hope for patients who haven’t responded well to existing medications.

The newer pathways for research further investigate the role of insulin resistance and metabolic dysfunction in Alzheimer’s, as well as exploring how GLP-1 agonists can protect neurons and improve brain health. They encourage the use of combination therapies, where metabolic treatments could be used alongside existing drugs or lifestyle interventions to create more care strategies [5]. This could lead to more effective treatments or preventive measures.

Societal Application

The topic of Alzheimer’s treatment definitely has an impact on everyday life and larger societal issues. This disease affects well-being of millions of people worldwide. As the global population ages, Alzheimer’s disease is becoming an increasingly intense concern because it strains healthcare systems and families who provide care for loved ones. Effective treatments could not only improve the lives of patients but also alleviate the emotional and financial burdens on caregivers.

Here are some questions to consider. How might advancements in Alzheimer’s treatment change our perceptions of aging? What if treatments targeting the brain’s metabolic processes, like insulin and GLP-1 therapies, could become as common as diabetes management? Could the future of Alzheimer’s care include personalized treatments based on genetic and metabolic factors?

The main message I want readers to remember is that while Alzheimer’s disease currently has no cure, research into treatments like insulin therapies, GLP-1 agonists, and amyloid-targeting drugs offer some hope for slowing progression and improving lives. These innovations not only provide new options for those with the disease but also open pathways for future treatment that could change how we approach aging and brain health.

References

[1] Podhorna, J., Winter, N., Zoebelein, H., & Perkins, T. (2020). Alzheimer’s Treatment: Real-World Physician Behavior Across Countries. Advances in Therapy, 37(2), 894–905. https://doi.org/10.1007/s12325-019-01213-z

[2] Severe Alzheimer’s Disease Study Group, Winblad, B., Kilander, L., Eriksson, S., Minthon, L., & et al. (n.d.). Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study. The Lancet, 367(9516), 1057–1065. https://doi.org/10.1016/S0140-6736(06)68350-5

[3] Liang, Y., Doré, V., Rowe, C. C., & Krishnadas, N. (2024). Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer’s Disease: A Systematic Review. Journal of Alzheimer’s Disease Reports, 8(1), 777–789. https://doi.org/10.3233/ADR-230181

[4] Parvin, S., Nimmy, S. F., & Kamal, M. S. (n.d.). Convolutional neural network based data interpretable framework for Alzheimer’s treatment planning. Visual Computing for Industry Biomedicine, and Art, 7(1), 3. https://doi.org/10.1186/s42492-024-00154-x

[5] Theisen, P. (2024). Alzheimer’s Association Board,of Directors. Early alzheimer’s detection can aid treatment, planning. Telegraph – Herald Retrieved from http://cordproxy.mnpals.net/login?url=https://www.proquest.com/newspapers/early-alzheimers-detection-can-aid-treatment/docview/3068907826/se-2

Health

Genetic Mutations and Concussions: A Hidden Risk Factor

Posted on February 17, 2025 by smohame4 / 0 Comment

Mild traumatic brain injury (mTBI), commonly known as a concussion, is one of the most frequent brain injuries, affecting millions of people each year. It often results from falls, sports injuries, or accidents, and symptoms may include headaches, dizziness, and trouble concentrating. Most individuals recover quickly within days or weeks, and medical professionals often reassure patients that symptoms will fade over time. [2]

But for some, recovery is not so simple. A significant number of people experience lingering effects, such as chronic headaches, memory problems, and emotional difficulties that can last for months or even years. The unpredictability of recovery makes it challenging for doctors to provide clear treatment plans, and factors like genetics, previous injuries, and individual health conditions can influence outcomes. This uncertainty can lead to frustration for both patients and healthcare providers.

Therefore, researchers are working to better understand why some people recover quickly while others struggle with long-term symptoms. By studying brain function, inflammation, and genetic factors, scientists aim to develop better treatments and personalized care strategies. Improving early diagnosis and management of mTBI could help reduce long-term complications and provide clearer recovery paths for those affected.

Figure 1[1]

The Role of Genetic Variants in mTBI Recovery

Mild traumatic brain injury (mTBI) affects millions of people, with most recovering within weeks. However, some individuals experience prolonged symptoms, and recent research suggests that genetic mutations may play a key role in this variability. Specific mutations in genes related to neuronal repair, inflammation regulation, and metabolic function can influence how the brain responds to injury. For instance, variations in the Apolipoprotein E (APOE) gene, particularly the APOE4 allele, have been linked to an increased risk of cognitive decline after repeated head injuries.[1]

Why Some Heal Faster Than Others

Certain genetic mutations may also heighten susceptibility to concussive trauma. For example, mutations in CACNA1A, a gene associated with ion channel function and migraine disorders, have been linked to an exaggerated response to brain injuries. These genetic factors affect everything from the brain’s initial metabolic crisis to long-term neurodegeneration. Understanding these mutations could help identify individuals at higher risk for severe or prolonged mTBI symptoms, leading to personalized concussion management and targeted recovery strategies.[3]

What role does this play?

The CACNA1A gene plays a key role in ion channel function, which affects neuronal excitability and communication.

The CACNA1A gene provides instructions for making calcium ion channels in neurons, which regulate brain signaling.
People with CACNA1A mutations may experience more severe responses to mild TBI, including increased swelling and cognitive issues.
This suggests that ion channel disorders could impact how the brain reacts to trauma, leading to worse long-term outcomes for some individuals.

The Future of Concussion Care: A Personalized Approach

Understanding the genetic basis of concussions doesn’t just impact athletes or military personnel—it has far-reaching implications for public health, workplace safety, and even everyday activities. If genetic testing could identify individuals more vulnerable to long-term brain damage, it could transform how we approach contact sports, car accident recovery, and workplace safety regulations. Imagine a future where concussion protocols are tailored to an individual’s genetic profile, reducing unnecessary risks and improving recovery outcomes. Should genetic screening become a standard part of concussion management? How might this knowledge shape policies in professional sports or even school athletics?

Figure 2[2]

Genetics may hold the missing piece in understanding concussions, and unlocking this knowledge could lead to breakthroughs in personalized medicine and brain injury prevention. As research progresses, the opportunity to protect those at risk grows stronger. Stay informed, advocate for better concussion awareness, and keep the conversation going—because the brain you protect today could shape your future.

Footnotes

[1] Bennett ER, Reuter-Rice K, Laskowitz DT. Genetic Influences in Traumatic Brain Injury. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 9. Available from: https://www.ncbi.nlm.nih.gov/books/NBK326717/

[2] Brain Treatment Center Newport Beach. (2024, September 16). Traumatic Brain Injury Treatment – Brain Treatment Center Newport Beach. https://www.braintreatmentnewportbeach.com/traumatic-brain-injury-tbi/

[3] McDevitt, J., & Krynetskiy, E. (2017). Genetic findings in sport-related concussions: potential for individualized medicine?. Concussion (London, England), 2(1), CNC26. https://doi.org/10.2217/cnc-2016-0020

[4] Conger, K. (2024, February 16). Concussion: Could your genes increase your risk? Scope. https://scopeblog.stanford.edu/2020/11/30/concussion-could-your-genes-increase-your-risk/

Disease/Health

Knowledge is Power OR Ignorance is Bliss?

Posted on February 16, 2025 by hdahlsei / 0 Comment

We’ve all seen the popular headlines: Breaking News, Alzheimer’s Disease is Now Type III Diabetes! But what does the research actually say?

Here is what we do know: Alzheimer’s is linked to insulin resistance, which is where the theory that the disease could be called type III diabetes comes from. But let’s back up and see exactly how related they are.

Neurofibrillary Tangles

When phosphorylation is increased or decreased, key signaling molecules for the insulin pathway are activated or inactivated. These include IRS, PI3K, Akt, and GSK-3β. These changes in the pathway can lead to insulin resistance, and overall insulin signaling dysfunction. Insulin resistance is the key way some research is connecting diabetes and Alzheimer’s. It leads to hyperphosphorylation of tau protein, which leads to neurofibrillary tangles [1].

Amyloid-β Plaques

Insulin resistance also can cause the formation and accumulation of amyloid-β plaques. Insulin competes with amyloid-β to be degraded by IDE and competes for binding sites on insulin receptors [1].

Neuroinflammation

Insulin resistance is interconnected with neuroinflammation, both of which are caused by pro-inflammatory cytokine release in the brain. Both can also lead to neurodegeneration. Additionally, neuroinflammation is thought to be another cause of amyloid-β plaque formation, further relating all of these factors [2].

Oxidative Stress

Insulin resistance is interconnected with oxidative stress as well. Insulin is known to boost, or worse, oxidative stress [1], and oxidative stress also can be a cause of insulin resistance [3].

Connection Alzheimer’s Disease

Neurofibrillary tangles and amyloid-β plaques have long been known to be key identifiers of Alzheimer’s. And, neuroinflammation and oxidative stress have been found to contribute to Alzheimer’s disease. Since insulin resistance has been connected to all of these factors, insulin resistance can be connected to Alzheimer’s disease [1].

Knowledge is Power

As we have seen, there are many ways in which insulin is related to Alzheimer’s disease, but it has not been definitively proven to be type III diabetes …yet. If this theory is further researched, and it turns out Alzheimer’s is type III diabetes, that could open the door for new research and treatment strategies. Diabetes medications or lifestyle changes could provide more options for Alzheimer’s patients and their families. People could learn about their lifestyle or genetic risk factors earlier, and have more time to gather information and make changes. If you have family members who have been diagnosed with Alzheimer’s, you could get tested, and make changes early on, that could potentially make a difference in the disease outcome. But would knowing you are at an increased risk for Alzheimer’s many decades down the road change your behaviors right now? Would more knowledge about how Alzheimer’s works in the brain, and how it’s connected to insulin and diabetes make you more likely to follow a doctor’s recommendations? What about if you knew the risk was in your family, but you didn’t know your own individual risk? Would you want to find more information? Would knowledge empower you to change your life?

Ignorance is Bliss

On the other hand, research shows that simply knowing genetic risk isn’t enough to change everyday behaviors [4]. Does this mean we need more education about how diseases work and why someone would need to make changes? Or is it that ignorance is bliss? Not knowing might allow you to not overthink, or stress out over something decades down the line. Since there is no complete cure and only treatments to slow the progression of the disease, there is not much you can do, and that might leave someone feeling powerless.

Both?

We definitely should focus research on this new theory, knowledge is power after all. However, we also need to make sure each individual has been given the choice of what information or tests they want to pursue. Because ignorance is bliss, both can be true at the same time. I, for one, just hope we have enough research on this topic to make informed decisions when we are at the age of risk.

References

[1] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135. https://doi.org/10.1016/j.neuint.2020.104707

[2] Vinuesa, A., Pomilio, C., Gregosa, A., Bentivegna, M., Presa, J., Bellotto, M., Saravia, F., & Beauquis, J. (2021). Inflammation and insulin resistance as risk factors and potential therapeutic targets for Alzheimer’s disease. Frontiers in Neuroscience, 15. https://doi.org/10.3389/fnins.2021.653651

[3] Hurrle, S., & Hsu, W. H. (2017). The etiology of oxidative stress in insulin resistance. PubMed Central, 40(5), 257–262. https://doi.org/10.1016/j.bj.2017.06.007

[4] Hollands, G. J., French, D. P., Griffin, S. J., Prevost, A. T., Sutton, S., King, S., & Marteau, T. M. (2016). The impact of communicating genetic risks of disease on risk-reducing health behavior: Systematic review with meta-analysis. BMJ, 352. https://doi.org/10.1136/bmj.i1102

Uncategorized

The Role Of Microglia And Astrocytes In inflammation

Posted on February 13, 2025 by smtesa / 0 Comment

Figure 1

Every year, an estimated 3.8 million concussions [1] occur in the U.S. alone, with many going undiagnosed. While these injuries may seem minor, new research suggests that even a single concussion can trigger long-lasting brain damage.

Concussions don’t just disrupt the brain; they set off a chain reaction of cellular and metabolic disruptions. This includes impaired energy production, protein accumulation, and chronic neurodegeneration. And when the brain experiences multiple concussions before fully recovering, the damage can become even more severe, increasing the risk of long-term cognitive impairment, Alzheimer’s disease, and Chronic Traumatic Encephalopathy (CTE). [2]

Therefore, understanding the long-term effects of concussions is critical, not just for athletes, but for anyone who may suffer a head injury.

The Brain’s First Responders: Microglia and Astrocytes in Inflammation

The brain is a highly protected organ, yet it is not immune to injury. When trauma occurs, the body’s immune system cannot send white blood cells past the blood-brain barrier. Instead, the brain relies on its own immune defense: microglia and astrocytes. These glial cells work to protect neurons, but their response to injury is sometimes not as favorable.

Initially, glial cells act as first responders, helping to contain damage. But if their activation is prolonged, they can contribute to chronic inflammation, leading to long-term neurological problems. Therefore, understanding how microglia and astrocytes function, and how we might regulate their response could be the key to developing new treatments for brain injuries.

Figure 2

Microglia: The Immune Warriors

Microglia are the brain’s resident immune cells, constantly monitoring their environment for damage or infection. When they detect a threat, they activate and shift into a pro-inflammatory (M1) state, releasing molecules as shown in figure 3 such as: [3]

Tumor necrosis factor-alpha (TNF-α)
Interleukin-1 beta (IL-1β)
Interleukin-6 (IL-6)

These inflammatory signals help clear debris and protect against infections, but if microglia remain overactive, they can contribute to prolonged inflammation, damaging healthy brain cells. As seen in Figure 3, prolonged inflammation in the brain can contribute to neurodegenerative diseases like Alzheimer’s and chronic traumatic encephalopathy (CTE).[6]

After a mild traumatic brain injury (mTBI), microglia are the first to respond. They rush to the site of injury and release these inflammatory molecules to clean up damage and protect the brain. However, sometimes they don’t shut off when they should, leading to long-lasting inflammation that can cause memory problems, mood changes, and increase the risk of future brain damage.

To heal properly, microglia need to switch into a repair mode (M2 state), where they release anti-inflammatory molecules like:

Interleukin-10 (IL-10)
Transforming growth factor-beta (TGF-β)

In this state, microglia help repair tissues and restore homeostasis.

Figure 3

Astrocytes: The Brain’s Support Network

While microglia act as the brain’s immune soldiers, astrocytes are more like engineers, they provide structure, support, and help keep the brain’s environment balanced. But after a brain injury, astrocytes change their behavior in a process called reactive astrogliosis . [4] This response helps protect the brain, but if it goes too far, it can cause problems.

When astrocytes become reactive, they:

Produce more glial fibrillary acidic protein (GFAP) – This helps form a protective barrier around injured areas, but too much can block nerve regrowth, making recovery harder.
Release inflammatory molecules (IL-1β, IL-6, MCP-1) – These signals attract more immune cells to the injury site, which can be helpful at first but may also prolong inflammation and damage healthy tissue.
Control neurotransmitters like glutamate – Normally, astrocytes remove excess glutamate to keep brain activity in balance. But after an injury, they can struggle to regulate it, leading to excitotoxicity, where too much glutamate overstimulates and kills neurons. [5]

Astrocytes and the Blood-Brain Barrier: The Brain’s Gatekeepers

In addition to supporting neurons and regulating inflammation, astrocytes play a key role in maintaining the blood-brain barrier (BBB), a protective shield that controls what enters and exits the brain. The BBB prevents harmful substances like toxins, bacteria, and inflammatory molecules from reaching brain tissue, while allowing essential nutrients to pass through. Astrocytes strengthen this barrier by releasing signals that help maintain its integrity.

After an mTBI (mild traumatic brain injury), astrocytes react to the damage, but this can have both helpful and harmful effects:
✅ Protective role – Astrocytes reinforce the BBB to prevent further injury and infection.
❌ Barrier breakdown – If inflammation is prolonged, astrocytes may fail to maintain the BBB, allowing harmful substances to enter the brain.

Figure 4

Potential Treatments for mTBI Recovery

Because both microglia and astrocytes play dual roles in brain inflammation—acting as both protectors and potential sources of harm—scientists are exploring treatments aimed at modulating their responses. Potential therapies include:

Microglia-targeted therapies: Encouraging microglia to shift from an M1 inflammatory state to an M2 repair-focused state. Minocycline, an anti-inflammatory antibiotic, shows promise in reducing prolonged inflammation [7]
Astrocyte regulation: Enhancing astrocyte function may improve glutamate clearance, reducing excitotoxicity and promoting neuronal survival. Certain drugs and omega-3 fatty acids may support this function.

A concussion isn’t just a quick shake it off moment; it’s your brain literally hitting the brakes and scrambling to recover. Microglia and astrocytes rush in like a cleanup crew, but if they overstay their welcome, they can cause more harm than good, leading to long-term brain issues.

So, give your brain the time it needs to heal. Rest, recover, and don’t rush back into action too soon. Pushing through too early can make things worse, but proper care can set you up for a stronger, healthier comeback. Your brain does a lot for you, make sure you take care of it, too!

Figure 5

Footnotes

[1] Hallock, H., Mantwill, M., Vajkoczy, P., Wolfarth, B., Reinsberger, C., Lampit, A., & Finke, C. (2023). Sport-Related Concussion: A Cognitive Perspective. Neurology. Clinical practice, 13(2), e200123. https://doi.org/10.1212/CPJ.0000000000200123

[2] Matthews,(2017). What is Chronic Traumatic Encephalopathy? | Saponara Brain & Spine Center. Www.saponara.com. https://www.saponara.com/what-is-chronic-traumatic-encephalopathy/

[3] Colonna, M., & Butovsky, O. (2017). Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annual review of immunology, 35, 441–468. https://doi.org/10.1146/annurev-immunol-051116-052358

[4]‌ Matusova, Z., Hol, E. M., Pekny, M., Kubista, M., & Valihrach, L. (2023). Reactive astrogliosis in the era of single-cell transcriptomics. Frontiers in cellular neuroscience, 17, 1173200. https://doi.org/10.3389/fncel.2023.1173200

[5] Michinaga, S., & Koyama, Y. (2021). Pathophysiological Responses and Roles of Astrocytes in Traumatic Brain Injury. International Journal of Molecular Sciences, 22(12), 6418. https://doi.org/10.3390/ijms22126418

[6] Postolache, T. T., Wadhawan, A., Can, A., Lowry, C. A., Woodbury, M., Makkar, H., Hoisington, A. J., Scott, A. J., Potocki, E., Benros, M. E., & Stiller, J. W. (2020). Inflammation in Traumatic Brain Injury. Journal of Alzheimer’s disease : JAD, 74(1), 1–28. https://doi.org/10.3233/JAD-191150

[7] Scott, M. C., Bedi, S. S., Olson, S. D., Sears, C. M., & Cox, C. S. (2021). Microglia as therapeutic targets after neurological injury: strategy for cell therapy. Expert opinion on therapeutic targets, 25(5), 365–380. https://doi.org/10.1080/14728222.2021.1934447

Uncategorized

Understanding Diffuse Axonal Injury (DAI) and Traumatic Axonal Injury (TAI)

Posted on February 12, 2025 by tchilala / 0 Comment

Diffuse Axonal Injuries: The Serious Brain Injury | Maryland Truck Accident Lawyer | The Poole Law Group

Introduction

Diffuse Axonal Injury (DAI) and Traumatic Axonal Injury (TAI) are serious brain injuries caused by traumatic events, such as concussions, car accidents, and falls. These lesions primarily impact the brain’s white matter, resulting in serious neurological deficits. This article dives into the fundamental principles that underpin these injuries, their clinical ramifications, and continuing research to improve diagnosis and therapy.

Summary of the Science

DAI and TAI develop as a result of shearing pressures applied to the brain during fast acceleration and deceleration, causing widespread damage to axons—the long fibers that connect neurons and promote communication within the brain.

Pathophysiology

1. Initial Mechanical Damage:

Upon impact, the brain undergoes rapid movement inside the skull, causing stretching and tearing of axons.
Mechanoporation, or the disruption of cell membranes, results in ionic imbalances, triggering a cascade of metabolic disturbances

2. Neurometabolic Cascade:

The injury leads to the indiscriminate release of glutamate, a neurotransmitter that contributes to excitotoxicity.
There is a subsequent increase in intracellular calcium, which impairs mitochondrial function and energy production (Figure 1).
An energy crisis ensues as ATP-dependent ion pumps work to restore homeostasis, leading to a temporary state of metabolic dysfunction.

3. Axonal Dysfunction and Disconnection:

Cytoskeletal proteins such as neurofilaments collapse, leading to axonal swelling and, in severe cases, disconnection.

Amyloid precursor protein (APP) accumulation at damaged sites is a hallmark of axonal injury, often detected via advanced imaging techniques like Diffusion Tensor Imaging (DTI) (Figure 2).

2.Secondary Injury Processes:

Inflammatory responses contribute to delayed cell death and chronic white matter degeneration.

Repeated injuries, especially within a vulnerable period, exacerbate neurodegeneration and long-term cognitive decline.

Clinical Implications

Patients with DAI or TAI present with a spectrum of symptoms depending on the severity of the injury. Common clinical manifestations include:

Mild cases include headaches, dizziness, memory problems, and impaired cognitive processing.
Moderate to severe cases include loss of consciousness, a lengthy coma, and considerable motor or cognitive impairment.

The susceptibility period following a first injury raises the chance of recurrent trauma, resulting in worse consequences. According to studies, metabolic recovery in humans might take weeks to months, needing ongoing monitoring before resuming to high-risk activities.

Advances in Diagnostics and Imaging

Diffusion Tensor Imaging (DTI) improves the detection of white matter alterations by tracking the flow of water molecules along axonal tracts.
Magnetic resonance spectroscopy (MRS) detects metabolic abnormalities, such as decreased N-acetylaspartate (NAA) levels, which are symptomatic of neuronal injury.
Biomarker research involves investigating blood-based indicators such as tau proteins and neurofilament light chains (NfL) for early diagnosis and prognosis.

Future Directions and Treatment Options

Neuroprotective Strategies: Therapies that address excitotoxicity, oxidative stress, and inflammation are being investigated.
Rehabilitation and Cognitive treatment: Individualized rehabilitation regimens that include physical treatment, cognitive exercises, and lifestyle changes aid in functional recovery.
Preventive Measures: New helmet designs and updated concussion protocols aim to reduce the impact of recurrent head trauma in contact sports and high-risk occupations.

Conclusion

Diffuse Axonal Injury and Traumatic Axonal Injury are severe types of traumatic brain injury with intricate underlying mechanisms. Advances in neuroimaging, biomarker studies, and targeted medicines offer hope for improved diagnosis and treatment of many disorders. Continued research is required to discover effective treatments and improve the results for afflicted people.

References

Giza, C. C., & Hovda, D. A. (2014). The new neurometabolic cascade of concussion. Neurosurgery, 75(S4), S24-S33.

Vagnozzi, R., et al. (2010). Assessment of metabolic brain damage and recovery following mild traumatic brain injury. Brain, 133(11), 3232-3242.

Johnson, V. E., Stewart, W., & Smith, D. H. (2013). Axonal pathology in traumatic brain injury. Experimental Neurology, 246, 35-43.

Disease/Health

Underneath the Helmet: What Happens to the Brain After a Concussion and Why Athletes Should Care

Posted on February 12, 2025 by Meg / 0 Comment

Concussions are a common type of traumatic brain injury that results from physical trauma to the brain, usually a hit, blow, or sharp jolt (Mayo Clinic Staff, 2022). But concussions are more than just a bump on the head, they trigger a cascade of complex biological processes that can have both immediate and long-term effects on the brain. The article “The New Neurometabolic Cascade of Concussion” (Giza & Hovda, 2014) highlights the pathophysiology of concussions, connecting how various physiological defects disrupt brain function and manifest themselves as symptoms.

In the United States alone, over 3.8 million sport-related concussions occur per year (University of Michigan Health, 2019), and its prevalence coupled with the potential for long-term effects, makes it a necessary area for research. For athletes, parents, and coaches, understanding this science is crucial to understanding the importance of proper recovery. The more we understand about concussions, the better we can prevent, recognize, and treat them.

The Neurometabolic Cascade: A Blitz in the Brain

When a concussion occurs, the brain undergoes a series of physiological changes known as the neurometabolic cascade. This process involves disruptions in ion balance, energy and metabolism, and cellular structure, which can lead to both short-term and chronic symptoms.

Ionic Flux

The initial trauma causes stretching and distortion of neurons, leading to tears in cell membranes. This allows potassium ions to flood out of cells and calcium ions to rush in, creating an ionic imbalance. This sudden depolarization triggers a wave of spreading depression. This is thought to be the biological basis for migraines as well, which likely explains symptoms of headaches, dizziness, and nausea.

Why does it matter for athletes?
Spreading depression can cause migraine-like symptoms like headaches, light sensitivity, sound sensitivity, and nausea. These symptoms are not just uncomfortable, but they’re also a sign that the brain is struggling to restore homeostasis.

Energy Crisis and Metabolic Dysfunction

To restore ion balance, the brain’s cells activate energy-dependent pumps, which require large amounts of ATP. This leads to hyperglycolysis, where the brain uses more glucose, which further depletes the brain’s energy reserves. At the same time, blood flow to the brain may decrease, creating a mismatch between energy supply and demand. This metabolic crisis can last for days or even weeks, leaving the brain vulnerable to further injury.

Why does it matter for athletes?
During this period of metabolic dysfunction, the brain is less able to handle additional stress. A second concussion during this time can increase damage and prolong recovery. This is why rest and taking time away from practice and games is so important!

Mitochondrial Dysfunction and Oxidative Stress

The influx of calcium into cells is particularly harmful to mitochondria. Excess calcium disrupts mitochondrial function, impairing ATP generation. This exacerbates the energy crisis and causes oxidative stress, which can persist long after the concussion.

Structural Damage: Axons and Cytoskeleton on Injured Reserve

Besides metabolic changes, concussions can cause physical damage to the brain.

Axonal Injury

The mechanical forces of a concussion can stretch and damage axons’ neurofilaments and microtubules, which is known as traumatic axonal injury (TAI). This damages the white matter in the brain, leading to symptoms like slowed processing speed, memory problems, and impaired reaction time.

Cytoskeletal Collapse

The cytoskeleton also may suffer injury. Calcium influx phosphorylates the cytoskeleton’s neurofilament side-arms leading to structural collapse. Injury to both axons and the cytoskeleton may alter neurotransmission, the way cells communicate with each other.

Why does it matter for athletes?
Even mild axon and cytoskeleton damage can impair cognitive and motor function, making it harder for athletes to perform at their best. Repeated concussions can compound the damage, increasing the risk of prolonged recovery or long-term deficits.

Inflammation and Chronic Risks

While inflammation is a natural response to injury, chronic inflammation can harm the brain. After a concussion, microglia become activated, causing inflammation that can damage neurons and disrupt brain function.

Why does it matter for athletes?
Chronic inflammation may contribute to persistent concussion symptoms and increase the risk of long-term neurodegeneration. Researchers are working to better understand this link to develop treatments to protect athletes’ brains.

From Sprint to Marathon: Acute Injury to Chronic Disease

The acute changes triggered by a concussion, such as ionic flux, energy crisis, and axonal injury can cause long-term problems.

Altered Protein Degradation and Aggregation
Concussions can disrupt the brain’s ability to clear damaged proteins, leading to the accumulation of toxic molecules like tau proteins. Oxidative stress can lead to dysfunction of the ubiquitin-proteasome system, which is necessary for normal protein degradation. These protein aggregates are a hallmark of chronic traumatic encephalopathy (CTE) and other neurodegenerative diseases.

Chronic Axonal Degeneration
Even after the initial injury, axons may continue to degenerate, leading to progressive brain atrophy and cognitive decline.

Cumulative Effects of Repeat Injuries
Repeated concussions, especially without adequate recovery time, can amplify all of the previously mentioned pathologies, increasing the risk of chronic impairment.

The science of concussions reveals just how vulnerable the brain is to injury, and even more so to repeat injuries. Starting with the initial ionic flux and continuing through the neurometabolic cascade, every concussion leaves a mark. For athletes, this highlights the importance of stopping play if a concussion is suspected, taking enough time to rest and recover, and working to prevent future injuries. By understanding the complex pathophysiology of concussions, we can better protect and treat athletes, keeping sports safe and fun.

References

Giza, C. C., & Hovda, D. A. (2014). The New Neurometabolic Cascade of Concussion. Neurosurgery, 75(Supplement 4), S24–S33. https://doi.org/10.1227/neu.0000000000000505

Mayo Clinic Staff. (2022, February 17). Concussion – Symptoms and Causes. Mayo Clinic; Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594

University of Michigan Health. (2019). Concussion in Athletes | Michigan Medicine. Uofmhealth.org. https://www.uofmhealth.org/conditions-treatments/brain-neurological-conditions/concussion-athletes-neurosport

Community/Disease/Health

Insulin signaling and Alzheimer’s disease

Posted on February 12, 2025 by rhurley1 / 0 Comment

The article we have covered this week, “Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease,” was an article about the correlation between the reception of insulin and Alzheimer’s. Basically, it works as following; insulin has to bind to a receptor along a phospholipid bilayer, and various chemicals (such as Grb2, MAP, and Kinases) must take their respective places to fulfill their roles, and then regular expression and regulation takes place. However, must that process fail, various things can go wrong to cause Alzheimer’s disease such as insulin resistance.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 that some of the distinguishable characteristics of Alzheimer’s disease are connected to both poor and abnormal insulin signaling. Though, the article specifically mentions neurofibrillary tangles and amyloid-beta plaques. As a result of this connection, we can now classify Alzheimer’s as the third type of diabetes by definition of diabetes.

Figure one from the article mentioned above^1 is specifically excellent at explaining insulin reception where it was needed (excellently timed, or in other words placed). This simultaneously is even a chart which shows what can go wrong, and spawn Alzheimer’s disease in the brain as a result. Although, it could feel scrambled if you’re not too familiar with the many acronyms in the Neuroscience field. This was an excellent piece to me for it is maximized simplicity, for clear reasons that kind of thing strongly helps. The figure may also benefit people uninvolved in Neuroscience as well because figure one works like a flowchart, and I find that effective myself in general because it’s easy on the eyes to track or logicate.

1. “Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease”

2. https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594