Sleep and Memory Consolidation

Sleep is an essential component of our daily lives, and it plays a critical role in our cognitive and emotional functioning. One important aspect of sleep is its role in memory consolidation – the process by which new information is transferred from short-term to long-term memory. In recent years, researchers have made significant advances in understanding the relationship between sleep, circadian rhythms, and memory consolidation. One particularly insightful paper on this topic is “Role of circadian rhythm and REM sleep for memory consolidation” by Zhengui Xia and Dan Storm.

The paper explores the complex relationship between sleep, circadian rhythms, and memory consolidation. The authors suggest that the circadian rhythm, which regulates the sleep-wake cycle, plays a critical role in memory consolidation. They propose that the timing of learning and memory consolidation can impact the effectiveness of memory formation, and that the circadian rhythm affects various aspects of brain function, including synaptic plasticity, gene expression, and neurotransmitter release.

CRE-Mediated Signaling

The paper referenced in this blogpost discusses the role of signaling pathways in hippocampus-dependent memory consolidation. The following paragraph summarises the section of the paper that discusses the role of CRE-mediated signaling in LTM consolidation: The process of memory consolidation is initiated by Ca2+ signals generated by NMDA receptors and is dependent on de novo transcription and translation. CRE-mediated transcription is strongly implicated in the consolidation of long-term memory (LTM) and integrates Ca2+ and cAMP signals. The CREB-binding protein, CREB, is implicated in LTM and other forms of neuroplasticity in mice and drosophila. Studies on mice show that stimulation of CRE-mediated transcription during training depends on activation of NMDA receptors and MAPK. Inhibition of CRE-mediated transcription by administration of CRE inhibitors to the hippocampus blocks memory formation, indicating the involvement of CRE-mediated transcription in memory consolidation.

REM Sleep

REM (Rapid Eye Movement) sleep is a stage of sleep characterized by rapid eye movements, low muscle tone, and vivid dreaming. It is one of the four stages of sleep, along with non-REM (NREM) sleep stages 1, 2, and 3. REM sleep is typically associated with heightened brain activity and increased heart rate and blood pressure. The authors delve into the role of REM sleep in memory consolidation. They suggest that REM sleep plays a critical role in the consolidation of emotional memories, procedural memories, and declarative memories. They propose that this may be due to increased activity in brain regions involved in memory consolidation, as well as increased levels of neurotransmitters such as acetylcholine.

The implications of this research are significant. A better understanding of the relationship between sleep, circadian rhythms, and memory consolidation could ultimately lead to more effective treatments for sleep disorders and cognitive impairments. For example, individuals with sleep disorders or cognitive impairments may benefit from interventions that target the timing and quality of sleep, or that enhance the activity of neurotransmitters involved in memory consolidation.

In conclusion, “Role of circadian rhythm and REM sleep for memory consolidation” provides valuable insights into the complex relationship between sleep, circadian rhythms, and memory consolidation. By understanding the neurobiological mechanisms underlying this relationship, researchers and healthcare professionals may be able to develop more effective interventions for individuals with sleep disorders or cognitive impairments.

What is Psychopathy?
Psychopathy is a personality disorder that is often characterized by a lack of empathy, impulsivity, and manipulative behavior. While there is still much to learn about the disorder, recent research has shed light on its neurobiological roots. In a paper published in the journal Molecular Psychiatry, researchers explore the genetic and environmental factors, brain regions, and neurotransmitters that may be implicated in psychopathy. They also suggest potential directions for future research and highlight the importance of better understanding the neurobiological mechanisms underlying the disorder.

The authors suggest that genetics may account for a significant portion of the variance in psychopathy, but that environmental factors such as childhood abuse and neglect may also play a role. They suggest that gene-environment interactions may be particularly important in the development of psychopathy. This highlights the need for continued research into both genetic and environmental factors that may contribute to the disorder.

Biology of Psychopathy

The researchers also discuss the brain regions and neurotransmitters that may be involved in psychopathy. Their results concluded that expression of ZNF132 and RPL10P9 is greatly reduced in neurons and astrocytes of habitually violent offenders. They also suggest that dysfunction in the prefrontal cortex, amygdala, and other brain regions may be implicated, as well as imbalances in neurotransmitters such as serotonin and dopamine. They also introduce a theory that states that a deficient opioid system may be implicated in psychopathy, which would explain why psychopaths tend to engage in drug abuse; to satisfy their reward system. This suggests that further research on the neurobiological basis of psychopathy could lead to a better understanding of the brain mechanisms involved in the disorder.

The authors highlight several potential directions for future research, including the need for more precise measurements of psychopathy, the use of animal models to study the disorder, and the development of more effective treatments. They suggest that identifying specific biomarkers of psychopathy could be particularly useful in developing more targeted treatments. Additionally, the authors suggest that a better understanding of the neurobiological mechanisms underlying psychopathy may have broader implications for understanding other psychiatric disorders.

Research on the neurobiological roots of psychopathy could ultimately have implications for reducing crime rates by identifying effective treatments for individuals who exhibit psychopathic traits and who are at higher risk of engaging in criminal behavior. Additionally, a better understanding of the neurobiological mechanisms underlying psychopathy could lead to more targeted interventions aimed at preventing the development of psychopathic traits in the first place, potentially reducing the number of individuals who engage in criminal behaviour.

In conclusion, the research on the neurobiological roots of psychopathy provides a valuable framework for understanding the disorder and may lead to new treatments and diagnostic tools in the future. Continued research in this area is critical to further our understanding of this disorder and to improve outcomes for individuals affected by it.

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It’s fairly well known that obesity can lead to an increased risk for numerous different health outcomes, such as type 2 diabetes and cardiovascular diseases. Obesity also causes a state of constant low-grade inflammation in the body, which in turn has it’s effects on the brain as well that people often don’t realize. Many thing’s go wrong in the body and brain that contribute to obesity, primarily an imbalance of energy homeostasis and hunger cues.

What’s Happening in the Brain

The hypothalamus region of the brain controls several endocrine functions that take metabolic feedback and regulate energy homeostasis. Basically, the hypothalamus will give signals to either increase or decrease hunger and energy use in response to the signals the body sends to the hypothalamus. Obesity can occur due to disorders of the hypothalamus, such as Prader-Willi syndrome. This is an inherited disorder that causes the hypothalamus to not recognize the sensation of being full when eating. This causes a constant urge to eat, and puts you are risk for obesity.

The Melanocortin System

The main player in this regulatory function is the melanocortin system. Insulin and leptin circulate the body in levels that are proportionate to the amount of adipose (fat) tissues, and the nutritional status of the body. These molecules bind to receptors in the melanocortin system and will decrease food intake, and increase energy usage.

In a healthy brain these cues are in balance, leading to a balance of energy usage and food intake. In obesity it’s been studied that there is a dysfunctional melanocortin system, leading to an increase of food intake and decreased energy usage.

Dietary Fats

Surely you’ve been told to eat the ‘right’ foods, and that fats usually aren’t those right foods. And maybe you’ve heard of ‘good’ fats and ‘bad’ fats, but what makes those different? The main two groups are saturated fatty acids (SFAa), and unsaturated fatty acids.

Saturated fats the ‘bad’ fats. They are typically solid at room temperature, meat and dairy products are the main dietary sources of these. Their structure consists of only single bonds, and have the maximum amount of hydrogen atoms in their structure. These fats are known to raise both good and bad cholesterol in the body, raising the risk of cardiovascular and other diseases.

Unsaturated fatty acids are the ‘good’ fats. These are more complex molecules, consisting of double bonds that cause bends in their chain. These fats are typically liquid or fluid like at room temperature. Common sources of these are oils such as vegetable or canola oil, nuts, and fish. These fats typically raise the level of good cholesterol in our body.

Effects of Fats in the Body and Brain

Studies have been done in rodents about the effects of certain fats on the hypothalamus. A diet with high amounts of SFAs have been shown to increase hypothalamic inflammation in days, while mono-unsaturated fatty acids did not compromise and hypothalamic function. SFAs have also been shown in these studies to cross into the brain and accumulate in the hypothalamus, where they block insulin and leptin signaling, and will disrupt the melanocortin system. It’s recommended that about 10-30% of our calorie intake should be fats, although only about 5-10% of caloric intake should be saturated fats.

References

1. https://my.clevelandclinic.org/health/articles/22566-hypothalamus
2. https://www.sciencedirect.com/science/article/pii/S2212877821000466
3. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/fat/art-20045550
4. “Hypothalamic Inflammation in Obesity and Metabolic Disease” A. Jais

What Are Endocannabinoids?

Endocannabinoids are naturally occurring molecules that are similar in structure to the active compounds in cannabis. These molecules are produced by the body and interact with the same receptors as THC, the main psychoactive compound in cannabis.

Structure

There are two main endocannabinoids: anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Anandamide has a chemical structure consisting of an ethanolamine head group, an arachidonic acid chain, and an amide bond linking them together. 2-AG, on the other hand, consists of a glycerol backbone with two arachidonic acid chains attached to it via ester bonds. Both endocannabinoids are synthesized on demand from membrane phospholipids and are rapidly metabolized to terminate their signaling effects.

Receptors

The two main receptors that are relevant to endocannabinoids are CB1 receptors and CB2 receptors. CB1 receptors are primarily found in the brain and central nervous system, while CB2 receptors are primarily found in immune cells and peripheral tissues.

Endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), bind to these receptors to regulate various physiological processes, including pain, appetite, mood, and inflammation. CB1 receptor activation is associated with the psychoactive effects of cannabis, while CB2 receptor activation is associated with anti-inflammatory effects.

Research has also shown that there are other receptors that can interact with endocannabinoids, such as TRPV1 receptors and GPR55 receptors. These receptors may have additional roles in mediating the effects of endocannabinoids in the body.

Signaling Pathways

CB1 and CB2, are G protein-coupled receptors (GPCRs) that are located throughout the body. When endocannabinoids bind to these receptors, they initiate a signaling cascade that leads to various physiological effects.

When an endocannabinoid binds to a CB1 receptor, it activates a G protein that can lead to the inhibition of adenylyl cyclase, which in turn reduces the production of cyclic adenosine monophosphate (cAMP). This leads to a decrease in the activity of intracellular enzymes such as protein kinase A (PKA) and mitogen-activated protein kinases (MAPKs), which ultimately results in the inhibition of neurotransmitter release from presynaptic neurons.

In addition, CB1 receptor activation can also lead to the activation of ion channels such as inwardly rectifying potassium (K+) channels and voltage-gated calcium (Ca2+) channels. This can result in the hyperpolarization of the postsynaptic membrane and a decrease in the excitability of neurons.

On the other hand, when an endocannabinoid binds to a CB2 receptor, it can activate several signaling pathways, including the inhibition of adenylyl cyclase and the activation of PI3K/Akt and MAPK signaling cascades. CB2 receptor activation can also lead to the inhibition of intracellular calcium release and the activation of potassium channels, which can contribute to the anti-inflammatory and immunomodulatory effects of endocannabinoids.

Endocannabinoids in Neurodegenerative Disease

The paper discussed in class highlights the potential roles of cannabinoid receptors in various diseases of the central nervous system (CNS). The authors describe the potential therapeutic benefits of targeting these receptors for the treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

The authors describe the endocannabinoid system as a key regulator of neurotransmitter release, synaptic plasticity, and immune function in the CNS. They discuss the role of CB1 receptors in regulating the release of neurotransmitters such as glutamate, GABA, and dopamine, and the potential therapeutic benefits of CB1 agonists in modulating these pathways.

The authors also describe the potential therapeutic benefits of CB2 receptor activation in the treatment of neuroinflammatory and neurodegenerative diseases, as well as pain and psychiatric disorders. They discuss the anti-inflammatory and immunomodulatory effects of CB2 receptor activation, as well as its potential role in regulating microglial activation and neurogenesis.

Artstract by Jessica Howard

Obesity can have multiple harmful effects on a person’s life. Most of us know mostly about the physical effects such as increased risk for heart disease. But there are also harmful effects to the brain, specifically the hypothalamus. The hypothalamus is the part of the brain in charge of homeostasis of the body using hormones. This includes, temperature regulation, energy expenditure, and eating habits. One important hormone that the hypothalamus uses to balance energy expenditure with calorie intake is insulin (Sateil & Olefsky, 2017).

How Energy is normally regulated

Normally, in the hypothalamus there are chemicals in the brain that control food intake and energy expenditure. The agouti-related peptide (AgRP) is inhibited by insulin while proopiomelanocortin (POMC) is activated by insulin. This causes the body to decrease its food intake while increasing its energy expenditure. AgRP expressing neurons normally activate melanocortin receptor expressing neurons (MC4R) which leads to increased food intake and decreased energy expenditure. POMC expressing neurons act as inhibitors of MC4R neurons which decreases food intake and increases energy expenditure. Insulin is an important part of keeping these two systems balanced for energy homeostasis (Sateil & Olefsky, 2017).

Salteil, A. R., & Olefsky, J. M. (2017). Hypothalamic inflammation in obesity and metabolic disease. The Journal of Clinical Investigation 127(1), 24-32. Doi:10.1172/JCI88878.

What Goes Wrong?

Obesity caused by a high fat diet activates stress signals in the hypothalamic neurons which release things called cytokines and other inflammatory responses. These responses lead to a decrease in sensitivity of the AgRP and POMC expressing neurons, this is also known as insulin resistance. This means that the neurons no longer respond as strongly to the presence of insulin. So AgRP neurons aren’t getting inhibited and POMC neurons aren’t getting activated, this means that there will be an increase in energy intake and a decrease in energy expenditure (Sateil & Olefsky, 2017).

One way which insulin is inhibited is by the activation of the MAPK pathway. This triggers the activation of JNK signaling which is a mediator of insulin receptor substrate proteins, which help transmit signals from insulin to create a cellular response (Shaw, 2011). In other words the JNK signaling inhibits insulin receptor substrate proteins by phosphorylating them, which deactivates them. This leads to insulin resistance in that cell. When this happens in AgRP neurons they are no longer inhibited and food intake increase, which then leads to more weight gain that serves to continue the insulin problem (Sateil & Olefsky, 2017).

Salteil, A. R., & Olefsky, J. M. (2017). Hypothalamic inflammation in obesity and metabolic disease. The Journal of Clinical Investigation 127(1), 24-32. Doi:10.1172/JCI88878.

What Can Be Done?

Obesity is a very serious condition that can cause great harm to all organs in the body, not just the brain. That is why it is important to seek treatment sooner rather than later. It is best to start with your doctor and get recommendations for a dietitian. A dietitian can help you create a meal plan that is balanced and healthy. It is also important to get regular exercise that with increase your heart rate, like swimming or fast walking. It can also be helpful to join a local weight loss group. This will offer you both a method of accountability and support from others facing similar challenges. It is also important to seek support from your family and friends. Tell them what you are trying to accomplish so that they can also help keep you accountable and keep you from any tempting situations. By sticking with your plan it is possible to lose weight and get better to live a longer healthier life (NHS inform, 2023).

References

NHS inform. (2023). Obesity causes and treatments. causes & treatments – Illnesses & conditions . Retrieved April 15, 2023, from https://www.nhsinform.scot/illnesses-and-conditions/nutritional/obesity#:~:text=The%20best%20way%20to%20treat,a%20local%20weight%20loss%20group

Salteil, A. R., & Olefsky, J. M. (2017). Hypothalamic inflammation in obesity and metabolic disease. The Journal of Clinical Investigation 127(1), 24-32. Doi:10.1172/JCI88878.

Shaw, L. M. (2011, June 1). The insulin receptor substrate (IRS) proteins: At the intersection of metabolism and cancer. Cell cycle (Georgetown, Tex.). Retrieved April 15, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142458/#:~:text=The%20IRS%20proteins%20are%20a,in%20response%20to%20insulin%20stimulation.

The Neurological Impact on Psychopathy

Psychopathy, or now more commonly known as antisocial personality disorder, in the simplest definition is the neuropsychiatric disorder that is commonly associated with deficient emotional responses, lack of empathy, aggression, manipulativeness, and lacking behavioral controls. This definition makes it clear that there must be some difference in the brains and/or genes of those with this disorder. Gene expression specifically has recently been linked to those with ASPD compared to those without. Genes that have been found in people with ASPD- RPL109, ZNF132, CDH5, and OPRD1 genes-have also been linked to genes found in those with autism. Similarly, there was findings that psychopathy is normally passed down from the father to son, possibly because of the XY genes of males compared to the XX gene in females. PEG10 is one paternally imprinted gene that was connected to the passing down of ASPD. Furthermore, another neurological change in those with psychopathic behaviors is related to dopamine release. Dopamine released from the cerebellum also has regulatory functions in social behavior. There is a connection between the cerebellum and antisocial behavior along with immune response-related pathways enrichment in those that express psychopathic behavior (1).

Diagnosis of ASPD

The overall consensus on how many people in the United States have ASPD is 1-4%. However, how does one determine this serious diagnosis? First, there are other antisocial disorders that have similar symptoms to ASPD. Borderline personality disorder includes unstable moods or manipulating behaviors, both overlapping with ASPD. Narcissistic personality disorder is diagnosed by looking for inflated sense of self-importance, which is also similar to those with ASPD. The only way to correctly differentiate between ASPD and other personality disorders is through behavior analysis by a psychiatrist or psychologist. People can begin developing ASPD traits in their early teen years or late childhood. This age makes diagnosis difficult because it can also be mistaken for ADHD, depression, or oppositional defiant disorder. Specific behavioral symptoms that a professional may look for during diagnosis is physical aggressiveness, reckless behaviors, blaming others, breaking the law, etc (2).

Is there a cure?

There is no cure. There is medication and therapy that may help the person control the effects of the disorder; however, there is no way to completely cure a person from ASPD. Therapy can include cognitive behavioral therapy that focuses on changing one’s thinking and behavior. Therapy can also include group therapy or family therapy. Family therapy could be important for the people that live with someone who has ASPD. ASPD does not just affect the person with the disorder, but also people around them, which is why it is so important to understand what the disorder entails. The stigma around having the disorder might negatively influence if people want to recognize it within themselves or want to get help (3).

Conclusion

Antisocial personality disorder has not been studied enough to where we have many long-term treatment options. However, new research is finding the links between this disorder and genes or neurotransmitter releases. Understanding brain chemistry is important in understanding what exactly causes such a behavior and possibly find more ways to diagnose the disorder.

Citations:

1. Tiihonen, J., Koskuvi, M., Lähteenvuo, M., Virtanen, P. L. J., Ojansuu, I., Vaurio, O., Gao, Y., Hyötyläinen, I., Puttonen, K. A., Repo-Tiihonen, E., Paunio, T., Rautiainen, M.-R., Tyni, S., Koistinaho, J., & Lehtonen, Š. (2019). Neurobiological roots of psychopathy. Molecular Psychiatry, 25(12), 3432–3441. https://doi.org/10.1038/s41380-019-0488-z
2. Antisocial personality disorder: Causes, symptoms & treatment. (n.d.). Cleveland Clinic. Retrieved April 5, 2023, from https://my.clevelandclinic.org/health/diseases/9657-antisocial-personality-disorder
3. Antisocial personality disorder – Diagnosis and treatment. (2023, February 24). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/antisocial-personality-disorder/diagnosis-treatment/drc-20353934
4. Types of personality disorders. (2018, November 12). Priory. https://www.priorygroup.com/mental-health/personality-disorder-treatment/types-symptoms-of-personality-disorders 
5. News, N. (2021, April 14). The neural basis of psychopathy. Neuroscience News. https://neurosciencenews.com/psychopahty-neural-basis-18234/