Cobbers on the Brain – Page 28 – Student Commentary on the Neurological Sciences

Imaginary Friends: Schizophrenia in Adolescents?

Posted on December 8, 2021 by / 0 Comment

Prevalence of Schizophrenia in Adolescents

Childhood-onset schizophrenia (COS) is very rare. It is only considered to be COS when diagnosed in children under 13, but full onset of the disease often does not occur until late adolescence or early adulthood. Although, if a child is experiencing hallucinations, delusions, or psychosis (more of which we will get into later) this can definitely be a cause for concern. It is important to understand that many children display unusual behavior; their brains are not even near to being fully developed! Also, before jumping the gun on schizophrenia, these symptoms can point to other psychiatric disorders such as depression, anxiety, and autism. A common worry that I have seen for parents is a child’s development of an imaginary friend. Is it an hallucination, a delusion, or simply a child with a healthy imagination?

What are Imaginary Friends?

Imaginary friends, also known as imaginary companions (ICs), have been seen throughout adolescent’s lives for years. It is by far not an uncommon phenomenon. Research even goes so far as to show that 65% of children up to age 7 experience an IC (Taylor et al., 2004). There are multiple reasons why adolescents may develop an IC:

Exploration
Companionship
Emotional support
Overcoming loneliness
Traversing relationships

Each of these reasons may be considered beneficial to a child’s development, rather than detrimental (Figure 1). Research has shown that benefits may include advanced social cognition, healthy coping strategies, superior emotional intelligence, and especially heightened creativity (Majors & Baines, 2017)! Imaginary friends can take any form that may be important to the child, whether that be a person, animal, or stuffed animal. More likely than not, ICs are a healthy aspect of child development, and it is important to understand the difference between imaginary friends and schizophrenic hallucinations.

Hallucinations and Delusions in Schizophrenia

Often times, parents either disregard the presence of an imaginary friend, or discourage the act altogether, due to worries in their child’s perception of reality (Majors & Baines, 2017). Although, as described above, ICs differ greatly from symptoms seen in schizophrenia such as hallucinations and delusions. Hallucinations can come in many different forms, including visual (sight), auditory (hearing), olfactory (smell), and tactile (feelings). In the case of schizophrenia, the individual does not understand these hallucinations are fake, and they are not in control. In children with imaginary friends, they most often understand that their friends are not real, and the child is in control of them (Fritz, 2015). Delusions are beliefs that do not align with reality. These include beliefs that someone is planning to harm them, beliefs that one is ill, beliefs that someone is in love with them, or beliefs that one is superior to others. Again, this is far different from a child’s development of an imaginary friend, as they are not out of touch with reality.

When to Take Action

A parent should become concerned if their child beings displaying these types of behavior (Fig. 2).

Hallucinations (as described above)
Delusions (as described above)
Disorganized speech or thought
Inappropriate or odd behavior for child’s age
Only speaks when spoken to; replying with short answers
Flat, monotonous facial expression

Beyond this, it is important to understand that schizophrenia in children is very rare. It is also a disorder of development, so major symptoms often do not show until late adolescence or teen years. Also, many of these symptoms correlate with other psychiatric illnesses that are not quite severe as schizophrenia, and often enough, they are just “symptoms” of being a developing kid. Although, if a parent is still concerned, it can never hurt to get a check-up!

Article Summary

Schizophrenia is a developmental disorder with a variety of positive and negative symptoms. The article focuses specifically on the role of the Wnt signaling, GSK3ß, and dopamine release. When there is an increase in dopamine, this inhibits Akt, leading to an increase in activation of GSK3ß. In regard to Wnt signaling, increases in dopamine also inhibit TCF/LEF-mediated transcription through the direct sequestering of ß-catenin. A primary treatment for schizophrenia, lithium, acts through the direct inhibition of GSK3ß, leading to an accumulation of ß-catenin and therefore, TCF/LEF-mediated transcription. There are also multiple genetic factors involved, primarily DISC1. DISC1 has been shown to inhibit GSK3ß, but it is dysfunctional in schizophrenia. Through this article, it appears as though the inhibition of GSK3ß, a decrease in dopamine release, and an upregulation of ß-catenin activation and TCF/LEF-mediated transcription are plausible targets for schizophrenia treatment (Singh, 2013).

References

Fritz, G. K. (2015). Imaginary friends . CABL, 31(5). https://doi.org/https://doi.org/10.1002/cbl.30041

Majors, K; Baines, E; (2017) Children’s play with their imaginary companions: Parent
experiences and perceptions of the characteristics of the imaginary companions and purposes served. Educational and Child Psychology , 34 (3).

Singh, K. K. (2013). An emerging role for Wnt and GSK3 signaling pathways in Schizophrenia.

Clinical Genetics, 83(6), 511–517. https://doi.org/10.1111/cge.12111

Taylor, M., Carlson, S. M., Maring, B. L., Gerow, L., & Charley, C. M. (2004). The
Characteristics and Correlates of Fantasy in School-Age Children: Imaginary
Companions, Impersonation, and Social Understanding. Developmental Psychology,
40(6), 1173–1187. https://doi.org/10.1037/0012-1649.40.6.1173

Disease/Health

Trauma Reminders: PTSD Triggers

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Development of PTSD Triggers

Post-traumatic stress disorder (PTSD) is a mental health disorder that develops after witnessing or experiencing a traumatic event. It has been found that memories of these traumatic events are often much stronger than the formation of non-traumatic memories (Reul, 2014). During the experience of traumatic events, the body enters fight-or-flight mode in which many normal body functions are halted, including working (short-term) memory. Due to this, the body becomes extremely vigilant, absorbing as much as they can about their current surroundings. The brain attaches smells, feelings, visuals, sounds, etc. to this event, storing them in long-term memory. Since this event is unable to be fully processed, the brain may cause recurring bouts of anxiety, known as triggers. These triggers are due to a combination of three memory processes:

Strong perceptual priming (exposure to a specific stimulus evokes a strong response to another stimulus).
Strong associative learning (strong relationship between two stimuli).
Poor memory elaboration (decreased ability to enhance an existing memory with new information) (Ehlers, 2015).

All of these processes are manifestations of underlying genetic and molecular changes in response to stressful events. Some of these changes include activation of the MAPK signaling pathway in the brain and subsequent gene transcription (c-Fos and Egr-1) that enhance traumatic memory stability (Reul, 2014).

Types of PTSD Triggers

Triggers are reactions that make one act as if their body is in danger, even though they harmless themselves. These can be experienced in many different ways:

- Panic attacks
  Figure 1
- Dreams or vivid memories
- Violence or aggression
- Increased startle response
- Substance abuse

PTSD triggers may be either internal or external. Internal triggers are those that one experiences within their body such as anger, pain, increased heartrate, muscle tension, and loneliness. External triggers are people, places, or things that one may encounter throughout their day. These include an anniversary date, a certain place, a movie or television show, a specific smell, or a person that serves as a traumatic reminder. Essentially, anything that reminds an individual of their traumatic experience may serve as a trigger.

Recognizing PTSD Triggers

It is important for one with PTSD to identify what their triggers may be in order to seek proper treatment. Due to the various reactions one may have to their triggers, and the amount of possibly triggering experiences, identification may be very difficult. It becomes especially difficult with sensory triggers, such as taste, smell, or touch. In order to determine one’s triggers, it is important to ask questions such as, “Where and when was I when my symptoms flared up?” or, “What was my experience during this flareup?”. Although, the primary and most beneficial way to discover one’s triggers is discussion with mental health professional.

Rob Tucker discusses how he realized he had PTSD:

https://www.youtube.com/embed/erVq2GJsMnM?feature=oembed

Coping Mechanisms

Interestingly enough, after identifying one’s triggers, repeated exposure to them is one of the most effective treatments, also known as prolonged exposure therapy. This allows one to remove that trigger from the traumatic experience, bringing it to the present where it no longer holds significance. Along with this, there are a variety of other coping mechanisms one may pursue:

Cognitive behavioral therapy (CBT)
Family therapy
Mindfulness and relaxation strategies
Medication
Group therapy
Emotional support animals

It is also imperative to stray away from unhealthy coping mechanisms, such as alcohol and drug use. The experience of PTSD triggers is a difficult and challenging one to overcome, but understanding their development, recognizing one’s triggers, and seeking help are the most important steps one can take.

References

Ehlers, A. (2010). Understanding and treating unwanted trauma memories in posttraumatic stress disorder. Zeitschrift Für Psychologie / Journal of Psychology, 218(2), 141–145. https://doi.org/10.1027/0044-3409/a000021

Reul, J. 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

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Signaling of the Endocannabinoid System

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Introduction to Endocannabinoids:

The endocannabinoid system is a complex biological system that helps to regulate various processes in the central nervous system. The endocannabinoid system plays a role in pain, memory, neuroprotection, and modulation of synaptic plasticity. The endocannabinoids are endogenous ligands that bind to CB1 and CB2 receptors in the brain and are produced via enzymatic degradation of naturally-occurring molecules. In English, this basically means that the endocannabinoids are produced by molecular scissors that cut off certain pieces of molecules that are already existing in the body. These newly-cut molecules then bind to the same receptors that are activated when one ingests marijuana. The endocannabinoids are responsible for regulating many things throughout the body, so I think it is important to discuss how endocannabinoid signaling works.

Endocannabinoid Signaling:

Endocannabinoids operate as retrograde messengers, meaning they mediate function on the pre-synaptic cell, rather than the post-synaptic cell. Endocannabinoid signaling begins the same way all neuronal signaling does—an action potential is sent through the neuron and a neurotransmitter is released. The neurotransmitter then binds to the post-synaptic cell, which allows for the influx of calcium into the post-synaptic cell. This is where endocannabinoid signaling differs from most other types of signaling. When calcium enters the post synaptic cell, endocannabinoids are released into the back into the synapse and bind to the CA1 and CB2 receptors (higher affinity for CA1 receptor, though). Once the endocannabinoids bind to their receptors, they can induce one of two things: depolarization-induced suppression of inhibition (DSI) or depolarization-induced suppression of excitation (DSE). The endocannabinoids induce DSE and DSI the same way, but which is induced depends on the type of pre-synaptic cell.

Depolarization-Induced Suppression of Inhibition

DSI is one result of endocannabinoid signaling. The CB1 and CB2 receptors are G-protein-coupled receptors (GCPR), which means they are associated with a G-protein. When the endocannabinoids are released from the post-synaptic cell and bind to the CB1 receptor, a complex signaling cascade occurs. The GPCR becomes a substrate for another enzyme called G-protein-coupled receptor kinases (GRK). GRKs are then targeted by beta-arrestin, which decouples the G-protein from the GPCR. Because the G-protein is uncoupled from the receptor, adenylyl cyclase is not activated, which then correlates with a decrease the levels of cyclic AMP (cAMP). The lowered levels of cAMP the inhibit calcium channels, thus decreasing the levels of neurotransmitters that are released, which opens potassium channels and causes hyperpolarization of the cell. In order for DSI to occur, the pre-synaptic cell has to be an inhibitory neuron. So, when the cell is hyperpolarized by the binding of endocannabinoids to the receptor, it suppresses the inhibitory effect of the pre-synaptic cell. This is a lot of information with a lot of acronyms, so I know it is easy to get lost. To try to help you understand DIS, I have included an image below that hopefully clears up any confusion.

Fig. 1. An image that shows the different steps of the endocannabinoid signaling cascade, including a description of what is happening. Drawn by H. Almlie.

Depolarization-Induced Suppression of Excitation

DSE is not much different from DSI. The exact same signal cascade occurs both DSE and DSI, so I will not go through the entire signaling cascade in words. There is a difference in which ion enters the post-synaptic cell, but this is a minor difference that doesn’t affect the rest of the cascade. The only major difference is the result of the hyperpolarization. In the DSI signaling cascade, hyperpolarization of the pre-synaptic neuron suppresses its inhibitory effects. In DSE, the endocannabinoids are acting on an excitatory pre-synaptic cell. So, when the cell becomes hyperpolarized, the excitatory effects of the pre-synaptic neuron are suppressed. A summary image of the signaling cascade is shown below.

Fig. 2. An image of the various steps of the endocannabinoid signaling cascade, including descriptions of what is happening. Drawn by H. Almlie.

Synaptic Plasticity:

I have discussed the signaling pathway of the endocannabinoid system so that it is easier to visualize how synaptic plasticity is modulated by the system. So, I described in detail how depolarization-induced suppression of inhibition occurs, which we can then transfer to depolarization-induced suppression of excitation. Through these two mechanisms, the endocannabinoid system modulates synaptic plasticity. DSI helps to strengthen neural pathways decreasing the amount of inhibition that pathway experiences. DSE helps to weaken neural pathways by decreasing the amount of excitation experienced by neurons in that pathway. So, DSE and DSI help to modulate synaptic plasticity by essentially doing the opposite of what those neurons usually do. In this way, endocannabinoids play an essential role in modulating synaptic plasticity within the central nervous system.

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Final Blog Post

Posted on December 8, 2021 by / 0 Comment

Last Blog Questions:

What kinds of learning occurred for you during this semester?
- I learned how to read, break down, and organize difficult scientific literature along with present to my classmates.
How do the skills, competencies, and knowledge gained in the experience (CAP, blogging) relate to your future goals?
- During the Community Action Project, I learned how to connect with the elderly population and collaborate with a team and other companies. The skills that I strengthened and developed during this project will help me with my future goals as I work with co-workers, patients, and other companies. My patients will consist of all ages, however, I wish to especially work with the elderly population, so this experience has helped me learn how to connect with them virtually and over the phone rather than just in person. This skill is important as I envision the future will consist of more virtual appointments and communication.
What does learning at a liberal arts institution mean to you?
- Learning at a liberal arts institution to me means that I have a well-rounded learning experience consisting of a diverse range of classes and topics taught. Smaller class sizes enable me to make connections with my professors and the majority of students within my area of study or interests. The liberal arts philosophy focuses not only on student success but student growth. Students at a liberal arts institution learn valuable skills within their area of study along with current and historical social justice issues.
If you were to highlight on your resume a skill or competency that you improved upon this semester, what would you be sure to include?
- I would highlight on my resume that I learned how to work better with a team and connect with other businesses along with participants of our project virtually.
Describe an example of solving a problem using several disciplinary perspectives.
- In this class, we learned how to solve the problem of not understanding concepts within scientific articles. To solve this problem, each student learned how to read, break up, and organize the article. The class then expressed their interpretations, questions, and misunderstandings to each other. These questions were collected and assigned to students to answer. After researching their assigned question each student would then present their findings to the class so other students could widen their understanding of the topic. Following the presentations, the students worked in small groups to work on remaining questions and misunderstandings together.

Disease/Health/Hot topics

The Endocannabinoid System: A Master Regulator

Posted on December 7, 2021 by / 0 Comment

Function of the Endocannabinoid System

The endocannabinoid system (ECS) was a mysterious being for quite some time, considering its recent discovery in only 1988. Although it is still in its infancy from a research standpoint, it is now known to be a major regulator with one primary goal: maintaining homeostasis. Many researchers consider the ECS to be the most important physiological system in establishing and maintaining human health. This is due in large part to the extensive network of cannabinoid receptors (CBR) located throughout the central nervous system (CNS), from neurons to immune cells to glands to organs. The ECS has been shown to be involved in many imperative processes:

Appetite and digestion
Neuroprotective effects of CB1R activation through GSK-3 inhibition (Snitow, Bhansali, and Klein, 2021).
Immune function and inflammation
Mood
Sleep
Reproduction/fertility
Learning and memory
Pain
Motor control

Due to the wide range of ECS functions and receptor activation, the use of endocannabinoids, specifically cannabis, have been implicated in the treatment of a variety of diseases. Some of these diseases include multiple sclerosis (MS), Alzheimer’s disease (AD), and Huntington’s disease (HD). This is due to the fact that activation of CB1R by endocannabinoids have been shown to promote neuroprotective effects (Kendall and Yudowski, 2017). It has been found that administration of THC increases phosphorylation of Akt in the hippocampus, striatum, and cerebellum, mediated by CB1R (as phosphorylation was blocked with CB1R antagonist). Along with this, THC was also shown to increase inhibitory phosphorylation of GSK3ß (Ozaita, Puighermanal, and Maldonado, 2007). GSK3ß inhibition is involved in the activation of Wnt signaling and its target genes, one of these genes being BDNF which is heavily involved in neuroprotection. Inhibition of GSK3ß is also involved cell proliferation and survival (Snitow, Bhansali, and Klein, 2021). The molecular underlying of CB1R activation through THC has shown to provide neuroprotective effects in battling neurodegenerative disease. Along with maintaining homeostasis, the ECS may be necessary for much more.

How does the ECS Work?

The ECS utilizes endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and enzymes to break down endocannabinoids. The endocannabinoids, 2-AG and anandamide (AEA), are retrograde ‘neurotransmitters,’ meaning they work from post to pre-synapse, rather than pre to post-synapse. Also, rather than being synthesized prior to use and stored in vesicles such as traditional neurotransmitters, endocannabinoids are rapidly synthesized upon demand. They are then released into extracellular space where they bind to a CBR on the pre-synaptic terminal (Lu and Mackie, 2016). There are two main types of cannabinoid receptors:

Crystal structure of the human cannabinoid receptor (Hua et al., 2016).

Cannabinoid Receptor 1 (CBR1) – a G-protein coupled receptor (G_i/o) abundant in neurons of the CNS (cortex, basal ganglia, cerebellum, and hippocampus)
Cannabinoid Receptor 2 (CBR2) – a G-protein coupled receptor (G_i/o) abundant in the immune system and associated structures

Some researchers hypothesize that there may be a third cannabinoid receptor as well. Although, these are likely widespread with each receptor having a specific function (Sallaberry and Astern, 2018). Lastly, the ECS has specific enzymes used to break down the endocannabinoids. AEA is primarily degraded by the enzyme fatty acid amino hydrolase (FAAH). A second degradation process may be through oxidation via cyclooxygenase-2 (COX-2) to form prostamides. 2-AG may be degraded by three hydrolytic enzymes: monoacylglycerol lipase (MGL) and alpha/beta domain hydrolases 6 and 12 (ABHD6 and 12). It may also be oxidized by COX-2, or under rare conditions, hydrolyzed by FAAH. MGL is the primary degrading enzyme for 2-AG (Lu and Mackie, 2017).

The ECS and Cannabis Use

The ECS interacts with both delta-9-tetrahydracannabinol (THC) and cannabidiol (CBD) in the marijuana plant, but in differing ways. THC is most similar to AEA, as they are both low-efficacy agonists of the CB1R (Lu and Mackie, 2017). Although, THC produces a high while AEA does not. This is due to the enzyme, FAAH, which breaks down AEA but is not able to break down THC. Therefore, THC acts as competitive inhibitor for the body’s natural endocannabinoids which produces a dramatic effect due to its psychoactive properties. Although, AEA has been shown to produce calming effects. Researchers believe CBD works through inhibiting the FAAH enzyme from breaking down AEA to produce a calm sensation without psychoactive side effects.

References

Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Frontiers in Cellular Neuroscience, 10. https://doi.org/10.3389/fncel.2016.00294

Lu, H.-C., & Mackie, K. (2016). An introduction to the endogenous cannabinoid system. Biological Psychiatry, 79(7), 516–525. https://doi.org/10.1016/j.biopsych.2015.07.028

Ozaita, A., Puighermanal, E., & Maldonado, R. (2007). Regulation of PI3K/AKT/GSK-3 pathway by cannabinoids in the brain. Journal of Neurochemistry, 102(4), 1105–1114. https://doi.org/10.1111/j.1471-4159.2007.04642.x

Sallaberry, C., & Astern, L. (2018). The Endocannabinoid System, Our Universal Regulator. https://doi.org/10.22186/jyi.34.5.48-55

Snitow, M. E., Bhansali, R. S., & Klein, P. S. (2021). Lithium and therapeutic targeting of GSK-3. Cells, 10(2), 255. https://doi.org/10.3390/cells10020255

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Perceptions of Obesity

Posted on December 7, 2021 by / 0 Comment

Introduction to Obesity

Heart disease is the leading cause of death in the United States, with approximately 660,000 people dying of this condition every single year.[1] Heart disease is a very broad term that includes many different types of specific heart conditions. The most common type of heart disease is coronary artery disease, which is characterized by the build-up of plaque in your coronary arteries.[2] This cardiac disease is most commonly attributed to poor lifestyle habits including a lack of exercise, smoking, and a poor diet.[3] Obesity is also a major contributor to coronary artery disease (and is a potential consequence of the aforementioned lifestyle habits).[4] Obesity is a prevalent problem around the world, but it is considered an epidemic in the United States due to its prevalence. In 2018, 42.4% of adults were considered to be obese in the United States.[5]

Now that you have some basic information about obesity, I would like to use my social studies knowledge to compare and contrast obesity it two different countries: America and Mauritania. I will compare how obesity is perceived in these two countries and the prevalence of the condition, just because I think it is interesting to analyze and learn about. After delving into the social science aspect of obesity, I will then dive into the neuroscience. We will dip our toes into the water of Lake Obesity before diving head-first into the deeper waters of said lake.

Obesity in America

I already discussed some of the statistics regarding obesity in the United States, so I will not rehash those. I will, instead, discuss the general perceptions and representation of obesity in America. As I stated previously, obesity in American society is pretty common. A little under half of the population is considered to be obese. Despite its prevalence, there are a lot of negative stereotypes that accompany the image of obese individuals. Individuals who are obese are often thought to be lazy, unintelligent, and weak-willed.[6] Many individuals believe that weight is something that should be in a person’s control, but those who are obese have simply failed at remaining in control of how much they eat and exercise.[7] As I will discuss in a later section, this belief is not entirely true (hint: neurochemistry is involved).

Many people are fighting the stigma of obesity by promoting “body positivity,” which is a movement that encourages people to love their own body, no matter their weight. It also encourages others in society to embrace those who have more weight, rather than ostracizing them. The movement is not meant to promote obesity, but it is more focused on people accepting their body and not letting others judge them based on their size.[8] There are also television shows that spread awareness of the obesity problem—showing the struggles of those individuals who are obese (the television programs tend to show the extreme cases of obesity). Though there are many stigmas surrounding individuals who are obese, our society is progressing (albeit, slowly) to see obesity as more of a societal issue, rather than an issue of an individual not being able to control their eating and exercising habits.

Obesity in Mauritania

I have discussed how obesity is generally viewed in America, but I now want to discuss how obesity is viewed in a country located in West Africa. I learned about this country and some of its traditional practices in eleventh grade when I took geography. In the country of Mauritania, obesity is seen in a completely different light, compared to America. Obesity has a lot of positive stereotypes in Mauritania. In fact, women purposely become obese because of what it means for them. Obesity is equivalent to wealth in Mauritania because being obese implies you have enough money to purchase an excess of food. Women are encouraged to become obese in Mauritania because it makes the more desirable and beautiful in the eyes of potential husbands. Obesity has many positive connotations in this West African country, and I think it is an important contrast to note. If you want to learn more about Mauritania’s “fat camp” (where girls are sent to gain weight), I HIGHLY recommend watching this video. Start the video at 10:09 to skip to the part about Mauritania. I have also included a drawing below of the stereotypes associated with obesity in both countries, just as a summary.

Fig. 1. An image comparing perceptions of obesity in American and Mauritania. Drawn by H. Almlie.

Neuroscience of Obesity[9]

Now that I have bored you to death by comparing how obesity is seen in two different countries, I want to give you whiplash and just talk a little bit about the neuroscience behind obesity. At the Thanksgiving dinner table, my dad asked a rhetorical question about why he feels full when he still wants to keep eating. Even though it was a rhetorical question, I answered his question. When you eat food, insulin and leptin receptors in your brain send signals to AgRP neurons and POMC neurons. AgRP neurons tell you to eat and POMC neurons tell you to not eat. So, when you are hungry, AgRP neurons are activated which encourages your body to intake food and limit energy expenditure. Meanwhile, the POMC neurons are inhibited, which means the signal to stop eating is not being sent. When you feel full, it is because the signals have switched so AgRP is being inhibited, while POMC is activated which is responsible for the “full” feeling you have after eating. In obesity, however, this signaling is altered. In obesity, the leptin and insulin receptors that are responsible for sending the signals to the AgRP and POMC neurons are resistant to their respective ligand. Because the receptors are resistant to their ligand, there is no regulation of the AgRP neuron, meaning your body is always receiving the signal to eat. This signaling cascade thus perpetuates the problem of obesity because you are not receiving the signal to stop eating. Jumping back to the section about obesity in America, this unregulated signaling is why obesity is not just simply a failure to control caloric intake—there are neurochemical changes going on in the brain that perpetuate the problem. The image below illustrates this neurochemical pathway and what is going on in obesity.

Fig. 2 An image that summarizes the neurochemical pathways of leptin/insulin signaling under normal conditions and obesity conditions. Image taken from https://moodle.cord.edu/pluginfile.php/1052912/mod_resource/content/2/inflammation%20and%20MD%202017.pdf

[1] https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm

[2] https://www.mayoclinic.org/diseases-conditions/coronary-artery-disease/symptoms-causes/syc-20350613

[3] https://www.mayoclinic.org/diseases-conditions/heart-disease/symptoms-causes/syc-20353118

[4] https://www.mayoclinic.org/diseases-conditions/heart-disease/symptoms-causes/syc-20353118

[5] https://www.cdc.gov/obesity/data/adult.html

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866597/

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866597/

[8] https://www.bbc.co.uk/bitesize/articles/z2w7dp3

[9] https://moodle.cord.edu/pluginfile.php/1052912/mod_resource/content/2/inflammation%20and%20MD%202017.pdf

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Sleep. The Best Part of the Day

Posted on December 7, 2021 by / 0 Comment

Sleep

When sitting in class and finishing work many individuals look forward to a specific time of the day. This is the time in which we can snuggle into our beds and fall asleep. However, is sleep more important than we think? Sleep provides healing and restoration and promotes good health and recovery from illness. Sleep is a cyclical physiological process that alternates with long periods of wakefulness. It influences physiological function and behavioral responses. This is controlled by your internal clock called your circadian rhythm. The part of your brain that controls the circadian rhythm is the suprachiasmatic nucleus (SCN) nerve cells in the hypothalamus control the rhythm of the sleep-wake cycle and coordinate this cycle with other rhythms.

Sleep Disturbance

There are some symptoms of the sleep cycle that cause disturbances and result in lack of sleep. These include anxiety, restlessness, irritability, and impaired judgement. However, is lack of sleep really that big of a problem? Lack of sleep can have serious potential problems for one’s health including high blood pressure, diabetes, heart attacks, and heart failure. The previous list of health problems relates to that of physical health, but what about the physiological perspective of the brain? When making memories it is important to note that there are three types of ways in which something can become a memory. This includes acquisition-learning or experiencing something new, recall-having the ability to access the memory in the future, and consolidation-the memory becomes stable in the brain. The first two are through to be done while an individual is awake, however, consolidation requires an individual to be asleep. This is because adequate sleep aids in the health of your hippocamps and neocortex within the brain. These areas while sleeping are believed to replay the events of the day and review/process memories and move them into an area where they can be stored as long-term memories.

Are there medical ways to help insomnia?

GABA are inhibitory neurotransmitters of the central nervous system that aids in sleep. GABA inhibitors are broken down into three different generations of hypnotics based on the GABA receptor mediated inhibitory process. These include the first- and second-generation hypnotics being barbiturates and benzodiazepines, while the third generation of hypnotics being imidazopyridines and cyclopyrrolones. The first- and second-generation hypnotics decrease waking, increase slow-wave sleep and enhance paradoxical sleep. Slow-wave sleep is the third phase of sleep which is the deepest phase of non-rapid eye movement sleep. During this time dreaming and sleepwalking can occur. This stage is also important for memory consolidation, which is a process where recently learned experiences are transformed into long-term memory. When paradoxical sleep is reached intense brain activity in the forebrain and midbrain occur. It differs from slow wave sleep due to the absence of motor function except for eye muscles and the diaphragm. An individual is unable to sleepwalk but is still dreaming during this time. The third generation of hypnotics is like that of the first- and second-generation hypnotics on waking and slow wave sleep but has a decreased paradoxical sleep during the first few hours of sleep.

How do benzodiazepines work?

By Hannah P.

Benzodiazepines are a class of drugs named for their chemical structure that are commonly used to treat anxiety disorders and sleep-related disorders. They include well-known drugs like valium, Xanax, and klonopin. There are dozens of drugs in the benzodiazepine class, but the mechanism by which they all exert their effects is thought to be similar. The sedating and anxiety-reducing effects of benzodiazepines are believed to be attributable to the drugs’ actions at receptors for the neurotransmitter gamma-aminobutyric acid (GABA). In particular, benzodiazepines act at a subtype of GABA receptors called the GABAa receptor; GABAa receptors that also bind benzodiazepines are sometimes called benzodiazepine receptors. When benzodiazepines bind, or attach, to the GABA receptor, they bind at alocation separate from where GABA itself binds and exerts an influence over GABA binding. This type of action is called an allosteric effect, and in the case of benzodiazepines it results in increased action at the GABA receptor. There is not complete consensus on exactly how benzodiazepine binding affects activity at the GABA receptor but there is evidence to suggest that it increases the likelihood that GABA binding will activate the receptor and/or increases the effect that GABA has when it binds to the receptor. That effect is to open an ion channel and allow the passage of negatively charged chloride ions into the neuron. This influx of negatively charged ions pushes the membrane potential further from zero, or hyper polarizes it, and makes it less likely the neuron will fire an action potential.This type of neural inhibition is the basis for the effects of benzodiazepines, for by inhibiting the activity of neurons that make up networks involved with anxiety and arousal, the drugs are able to produce calming effects.

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Understanding Marijuana and Your Brain

Posted on December 7, 2021 by / 0 Comment

Featured Image: The cycle a marijuana addicted brain will enter as the need for more and more weed is required to reach the same “high”. The mechanism is possibly mediated by an increase in go signals (as Glutamate) that increase the synthesis of dopamine (pleasure chemical). Dopamine is one of the chemicals produced that cause the pleasurable emotions associated with marijuana. Artstract by Alison Amundson.

Marijuana Use

18 states have legalized weed and has become the most commonly used federally illegal drug in the United States. Figure 1, shows which states have legalized marijuana and the type of product that is legal. About 18% of Americans have used marijuana at least once. There has been a steady increase of marijuana use in

**Figure 1:** https://www.ncci.com/Articles/Pages/Insights-2021-Marijuana-Legalization-Update.aspx

young adults and adolescents since 2019. In 2017, 24% of 12^th-graders had used marijuana in the past year and in 2019, the percentage increased to 35.7%.

With more and more people using marijuana the need to fully understand its mechanisms is becoming increasingly important.

Cannabinoids

Cannabis contains over 500 natural compounds, including cannabinoids, terpenoids, flavonoids, and alkaloids. The primary psychoactive agent is -tetrahydrocannabinol (THC). This ingredient is what has promoted the widespread recreational use of marijuana. THC is defined as a cannabinoid and acts on the endocannabinoid system (ECS) of the brain.

The brain produces its own cannabinoids known as endocannabinoids. Both cannabinoids and endocannabinoids act on cannabinoid (CB) receptors. The primary receptor in the brain is CB1, it is this receptor that mediates the effects of THC. CB2 receptors are predominantly found in peripheral systems of the body, as displayed in Figure 2.

**Figure 2**: https://www.drgreenrelief.com/blog/endocannabinoid-system-cb1-cb2-receptors/

CB1 is expressed in the cortical areas involved in higher cognitive functions, midbrain regions associated with motor control, and hindbrain regions that participate in control of motor and sensory functions of the autonomic nervous system. Therefore, marijuana has the potential to vastly affect the brain in a multiplicity of methods.

CB2 receptors are expressed in the midbrain ventral tegmental area on dopamine neurons. It is postulated this region is where the addictive properties of marijuana are modulated.

**Figure 3:** doi: 10.3389/fncel.2016.00294

THC and the Brain

Figure 3 is a proposed schematic of CB1 receptor activation at the synapse of a neuron. The depth this image provides to CB1 signaling is too vast for such a small blog post. However, it does show that an agonist of CB1, like an endocannabinoid (2-AG or AEA) or a cannabinoid (THC), decreases cAMP activity, inhibits Ca²⁺ channels, decreases the release of neurotransmitters (such as GABA), and opens K⁺ channels causing hyperactivity.

Consuming marijuana increases the amounts of agonists available to bind to CB1 receptors. An important note here is THC is only a partial agonist of CB1, thus the mechanism of THC on CB1 is more complicated. THC being a partial agonist lends to the complexity of THC’s effects on the brain and why scientists have not yet figured it out.

An interesting theory suggests that THC lasts longer and is present in greater amounts than our endocannabinoids, thus overwhelming the self-regulating system. THC inhibits the production of GABA, the ‘stop’ signal for dopamine synthesis. Therefore, the ‘go’ signal for dopamine synthesis (glutamate) becomes dominate and dopamine is over-synthesized. Dopamine is associated with pleasure and reward. This mechanism is suggesting that the effects of THC on the brain are due to an increase in dopamine synthesis and release.

Final Points

The precise mechanism of THC, the main psychoactive ingredient of marijuana, is not well defined. Thus, it cannot be definitively stated that marijuana is bad for you. Nevertheless, the widespread increase in marijuana use should not be encouraged until we have a full, clear view on this substance.

References:

https://www.cdc.gov/marijuana/data-statistics.htm

https://drugabusestatistics.org/marijuana-addiction/

https://www.drugabuse.gov/publications/research-reports/marijuana/what-scope-marijuana-use-in-united-states

https://www.frontiersin.org/articles/10.3389/fncel.2016.00294/full

doi: 10.1080/00952990.2019.1634086

Health

Lights Out on Light Sleep

Posted on December 7, 2021 by / 0 Comment

Night time light exposure is seemingly common. From working into the night hours to binge watching your favorite Netflix series, we are constantly bombarded with blue light exposure at night. The exposure to constant light does not come without a cost. Humans were made to function and follow an intelligent circadian rhythm. One that allows us to feel energized and ready to take on each day, and ready for a good night’s rest at night. Our circadian rhythm is highly regulated through the use of light. With light in the morning helping us to suppress melatonin and wake up, while in darkness in the evening to help us get tired before bed. What happens when we disrupt this natural rhythm? How does our sleep change and body respond?

What’s the Cost?

During the night, humans undergo processes of REM and NREM sleep. However, if this is fragmented, daytime functioning is impaired and increased sleepiness occurs. This has further implications on human health including disruption of metabolism, cardiovascular function, mental health, and even cancer risks. In particular, artificial light at inappropriate times, specifically light at night and exposure to light from mobile devices like phones, computers, and tablets is known to cause this disruption in addition to poor performance, insomnia, emotional disturbances, and gastrointestinal issues.

It has been shown that short-wavelength light (470nm or lower) is associated with a decrease in melatonin, reduction in reaction times, and depression in sleepiness, as well as changes in EEG power in the delta-theta frequency range. The cognitive effect of light is increased in alertness. Disruptions in our natural circadian rhythm can cause disruptions in our ability to have REM sleep, which is needed for memory consolidation and learning abilities.

Dim Light at Night Impact

Studies have been done to test the impact dim light at night has on the ability to sleep and produce locomotor activity in rats and mice. Protocols in animals being exposed to dim light at night, during their normal dark phase, has shown to reduce locomotor activity levels, and in rats, studies show that there is a decreased amplitude of daily rhythms of REM and NREM sleep, in addition to specific changes in the NREM EEG spectra around 16-19Hz.

The figure below shows the impact of light (in different forms) on circadian rhythms, sleep, arousal, and cognitive function. As the figure shows, dim light at night results in a decrease in locomotor/ exploratory activity, a decrease in amplitude of activity rhythm, and a decrease in amplitude of mPER1/2 rhythms. There is also a decrease in the amplitude in REM and non-rapid eye movement rhythms. Likwise, there is also a decrease in spatial performance, and increase in both anxiety-related behavior, and depression-related behavior.

Likewise, another study found that while any light can suppress the secretion of melatonin, specifically blue light at night will cause more of a powerful effect. It was shown that blue light suppresses melatonin about twice as long as green light, while shifting circadian rhythms twice as much.

Overall, blue light impacts our ability to get a good night’s sleep, through REM sleep, which is vital for our health and wellness. Prioritizing restful sleep through avoiding light and following our natural circadian rhythm is important for human’s health.

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Neurodegenerative Diseases: Is Cannabis the Answer?

Posted on December 7, 2021 by / 0 Comment

Background:

Endocannabinoids are gaining media exposure as many states are legalizing the recreational and medicinal use of marijuana, which contains the numerous endocannabinoids, the two most commonly mentioned are CBD and THC. Endocannabinoids are signaling molecules that are naturally made throughout the body, including the brain, that act as signaling molecules for various processes: stress, cognition, immunity, pain, eating, anxiety, reproduction, growth, and metabolism. Endocannabinoids are synthesized from fatty acids in the phospholipid bilayer of the post-synaptic neuron when calcium concentrations rise due to too much excitatory signaling. The two main endocannabinoids synthesized in the brain are AEA (N-arachidonoylethanolamide) and 2-AG (2-arachidonoylglycerol). Once the endocannabinoids are synthesized, the molecules are then released and can bind to CB1 and CB2 (G-protein coupled receptors) receptors to set off various signaling cascades.

Endocannabinoid Receptors:

AEA and 2-AG readily bind to CB1 receptors, which are highly concentrated in the brain and even throughout the rest of the body. Most often, these ligands inhibit the release of neurotransmitters in the presynaptic cell to tell the neuron to stop releasing neurotransmitters as a retrograde signaling cascade. The neurotransmitters that AEA and 2-AG typically inhibit dopamine and glutamate from being released from the pre-synaptic neuron to stop excitatory signaling.

AEA and 2-AG can also bind to CB2 receptors, which are found in cells that have immune functions. CB2 receptors are often found on microglia, which are responsible for producing inflammatory and anti-inflammatory cytokines in the brain. One interesting finding is that CB2 receptors have been found to be downregulated or malfunctioning in some neurodegenerative diseases including Multiple Sclerosis and Alzheimer’s Disease.

Figure 1: Artstract by Lauryn L Hinckley

Signaling Pathway:

The CB1 and CB2 receptor activation via THC has shown great promise in activating the MAPK/PI3K, which ultimately activates BDNF or brain-derived neurotrophic factor, as seen in Figure 2. BDNF is responsible for promoting life-sustaining roles that include neurogenesis, synaptic plasticity, and neuroprotection. Neurogenesis slows down with aging and can also account for a more difficult time learning, as well as reduced synaptic plasticity due to decreased activation of BDNF. However, it is interesting to think about THC improving the synthesis of BDNFs to improve cognition and memory, as well as have neuroprotective factors. Thus, THC is currently being studied as a potential treatment for neurodegenerative diseases and traumatic brain injuries.

THC is also an antioxidant, which could help to reduce amyloid beta plaques and hyperphosphorylation of tau. On the other hand, consuming a diet high in fruits and vegetables could also provide antioxidant properties as consuming THC to help manage age-related diseases and produce neuroprotective factors.

Side effects:

Consuming cannabis is not without side-effects. Some studies have demonstrated that marijuana can be addictive, approximately 9% of all people who use the substance will lead to a dependence. However, those who use cannabis in their teens can see a heightened dependence rate of 17%. Teenagers who use cannabis can also experience a decline in IQ and increased mental health issues.

Another alarming side effect of cannabis use is the interaction with other drugs, especially anesthetics. Users of cannabis require four times the amount of Propofol during surgery than those who do not use cannabis. Propofol can interact with both CB1 and CB2 receptors to reduce the release of dopamine, norepinephrine, and epinephrine and increase GABA release. THC has the exact opposite effects of Propofol. Increased amounts of anesthetics can increase the risk for adverse side effects. More research needs to be done to understand the negative impacts of THC exposure and anesthetic interactions.

So what?

More research needs to be done on cannabis and the endocannabinoids that it contains. Cannabis is a Schedule I Drug, so it is incredibly difficult and expensive to study. New research is hard to attain due to this classification, yet legalization of recreational and medicinal use is becoming more and more common in the United States. Thus, cannabis use for studies should also become more readily available to educate users and work to better understand how cannabis can be used to treat neurodegenerative illnesses.

Sources: