Cobbers on the Brain

The endocannabinoid system (ECS) is mainly found in the central nervous system (CNS) and plays important roles to modulate plasticity and homeostasis in the brain. When we talk ECS, the major receptors for binding are CB1 and CB2 receptors and the two main endocannabinoids are 2-AG  and anandimide   [1]

The CB1 receptor is known to be the most abundant GPCRs in the CNS and does the function of inhibiting the release of both excitatory and inhibitory neurotransmitters. The CB1 receptor also binds the many ligands, including the notable THC, AEA, and 2-AG. THC is an active ingredient in marijuana and can elicit feelings of calm, just like endocannabinoids. However, endocannabinoids are naturally produced by the body.

While CB1 receptors are abundant in areas like the hippocampus and neocortex, CB2 receptors are found in areas such as cells and tissues of the immune system. CB2 receptors are also localized to the microglia, which relates to neuroinflammation in the CNS. Neuroinflammation also relates to diseases such as Alzheimer’s disease (AD), which is a huge area of research today. [2]

Now endocannabinoids. These are natural chemicals that are produced by the body. They interact with the cannabinoid receptors in the CNS, and affect process relating mood, memory, appetite, and pain sensation. These molecules are similar to the compounds found in the cannabis plant, which is they are called “endocannabinoids” meaning cannabinoids produced inside our bodies.

Societal stereotypes have taught us to associate cannabis with words like addiction, failure, druggie, crazy, and many other negative words. It is agreeable that the feelings of calmness induced by cannabis may lead to high risks of addiction, but did you know that cannabis may also hold some potential in increasing the quality of health when used appropriately? Currently, only the University of Mississippi is allowed to conduct research with cannabis. This confirms the existing research gaps in this area.

Relating this to AD, preclinical studies in animal studies have shown that modulating the endocannabinoid system can have neuroprotective effects, reducing inflammation and oxidative stress which are implicated in AD. Researchers also believe that the endocannabinoid system may serve as a  therapeutic target to provide pharmacological benefits for AD. The neuroprotective effects of endocannabinoids may be due to interference with several cellular and molecular mechanisms, including apoptosis and inflammation. The progression of AD is related to the changes in the endocannabinoid system. Both cannabinoid receptor agonists and endocannabinoids, such as AEA, can reduce the neurotoxicity caused by Aβ-peptide in a mitogen-activated protein kinase (MAPK) pathway. [3]

Figure 1. Diagram showing the binding action for the two main endocannabinoids in the body, 2-AG and AEA. [4]

Figure 2. Diagram explaining the binding action for CB1 and CB2 receptors. [5]

Figure 3. Artstract by student depicting how stereotypes and uncertainties around cannabis hold back research on how cannabis might improve human health.

References.

[1] Zou, S., & Kumar, U. (2018, March 13). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International journal of molecular sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/#:~:text=As%20the%20two%20major%20endocannabinoids,D%20(NAPE%2DPLD).

[2] Kendall, D. A., & Yudowski, G. A. (2017, January 4). Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Frontiers in cellular neuroscience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209363/

This blog post will focus on the interesting intersection between anxiety and memories. I personally found this fascinating because before discussing this in class, I never considered how memories of past events register in our brains, and how these events translate into trauma. I mostly investigated this topic from a psychology perspective but what does neuroscience have to say about this topic?

The brain’s ability to remember things is very important for our daily lives. Memories help us navigate the world, both physically and socially. They also help us adapt to changes and prepare for similar situations in the future. Sometimes, really stressful events can leave a lasting impact on our memory, especially if they’re traumatic.

Figure 1. Diagram showing past events that could potentially lead to cases of anxiety disorders such as Post Traumatic Stress Disorder (PTSD) [2]

Research using animal models suggest that stress affects learning and memory processes in the brain, particularly the hippocampus. Stress-induced hormones enhance memory formation, which can be observed in various behavioral tests like the forced swim test. This test involves placing rodents in water where they show an immobility response, which is considered a learned behavior. Drugs that increase neurotransmitter levels can affect this behavior, making it an important tool for antidepressant drug screening. Glucocorticoid hormones play a crucial role in memory consolidation, particularly through the action of the glucocorticoid receptor in the hippocampus. This receptor is essential for the acquisition and consolidation of memories associated with stressful experiences. [2]

Looking into more of the neuroscience, the roles of glucocorticoid hormones as well as histone modifications are crucial in the brain’s response to stress. Studies found that stress-induced changes in specific histone marks in neurons of the hippocampus, a brain region involved in memory and stress response, were associated with increased transcription of certain genes. These changes were observed after exposure to psychological stressors like forced swimming and novelty but not physical stressors like cold exposure.

Another interesting knowledge on this topic is the role of the HPA axis  in responding to stress. The release of cortisol regulated by the HPA axis (hypothalamic-pituitary-adrenal axis) and begins with the release of CRH from the hypothalamus. Cortisol is a glucocorticoid. Cortisol acts on glucose metabolism to maintain normal glucose levels especially during times of stress. [3]. Fluctuations in cortisol secretion often accompany psychiatric disorders, and normalization of its levels correlates with improvement in a patient’s health. This also means that cortisol may be useful as a biological marker that can help determine the likelihood of a mental illness, its onset, and the severity of symptoms. [4]

Figure 2. Schematic representing the brain’s response to stress [5]

References.

[1] Matthew Tull, P. (2021, April 21). How traumatic events cause PTSD. Verywell Mind. https://www.verywellmind.com/ptsd-causes-and-risk-factors-2797397

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

[3] Chourpiliadis, C. (2023, July 17). Physiology, glucocorticoids. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK560897/

When we talk about tumors, they can grow and exist differently. There are canceorus (malignant) tumors and non-cancerous (benign) tumors. A tumor is a solid mass of tissue that forms when abnormal cells group together. They can affect different parts of the body including the bone, skin, tissue, and organs. Factors that increase the risk of developing a tumor include gene mutations, smoking, family history of certain types of cancer and smoking. [1]

Glioblastomas (GBM) are brain tumors that affect the normal intracellular and intercellular signaling for the advantage of the tumor cells but to the disadvantage of the whole organism. Some of the subtypes of glioblastomas include classical GBM, mesenchymal GBM, proneural GBM, and neural GBM.

GBM can also occur as a primary tumor or a secondary tumor developing from pre-existing lower grade tumor glioma tumors. Primary GBM develop very quickly, without evidence of preexisting symptoms while secondary GBM develop from a lower grade tumor. Some of the common symptoms of glioblastomas include perisistent headaches, double or blurred vision, vomiting, new onset of seizures, changes in mood and personality. [2]

To delve more into the neuroscience of cellular processes involved in GBM, the Mitogen- activated protein kinase (MAPK) signaling and pathways are interrupted in GBM. This can affect functions such as cell survival. The MAPK pathway contains three activated protein kinases that are key components of a series of vital signal transduction pathways and regulte regulate proceses such as cell proliferation, cell differentiation, and cell death. Below is a diagram showing the MAPK pathways. [3]

Figure 1. Diagram showing the major MAPK pathways (cascades) in mammalian cells [4]

Think of the MAPK pathway like a chain reaction in your body’s cells that gets started when certain growth factors, like epidermal growth factor (EGF), bind to their special receptors on the cell surface. These receptors are like switches that turn on the pathway. When the growth factor binds to the receptor, it causes the receptor to team up with other proteins inside the cell, like GRB2 and SOS. These proteins then pass signals along to another protein called Ras, which acts like a messenger. Ras gets activated and starts a series of events that ultimately lead to the activation of MAPK, a protein that helps control cell growth and division.

In cancer, this pathway can go haywire. Sometimes, certain genes like the one for the epidermal growth factor receptor (EGFR) get too active, causing the MAPK pathway to go into overdrive. This can make cells grow and divide uncontrollably, leading to tumor growth and making the cancer more aggressive.

Figure 2. Cartoon schematizing the crostalk between glioblastoma cancer stem cells (GSCs) and major cellular components of glioblastoma tumor environment.

References.

[1] Professional, C. C. medical. (n.d.-a). Tumor: What is it, types, symptoms, treatment & prevention. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21881-tumor

[2] Jigisha, T., Pier, P., & Vikram, P. (n.d.). Glioblastoma multiforme. AANS. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Glioblastoma-Multiforme

My time at Concordia has been filled with thrill, lessons, failures, self-discovery, and many events that sneaked into my life unknowingly. However, did I enjoy it? Absolutely! Reflecting on my freshman year when I was not aware of the many events that lay ahead of me, I look back and my younger self and whisper: “You can do this, you will make it”. My younger self in my freshman year was very timid and scared of the things I was not used to, especially in academics. However, looking back I am glad to have gained so much from a liberal arts education here at Concordia. I will highlight specific events that had the greatest influence in my life.

First, Covid. The pandemic taught me a lot of things especially since it happened during a time I was learning independence. Working independently to take care of myself and school in the midst of a pandemic taught me the importance of resilience, communication, and outreach. I was able to navigate through this transition by holding conversations with people who I learnt from, watching people around me grow, and learning to be patient with myself.

Second, self discovery. I learnt a lot of things I did not know about myself before college. Most of them, I realized from hearing people voice out my strengths and weaknesses. This encouraged me to recognize my strengths and embrace my weaknesses. Failures from difficult classes revealed ways of building my weaknesses using my strengths and I am grateful for every moment. I am still discovering myself everyday and I am sure it will be a life long process. However, I will continue to travel this path of opportunity with gratitude in my heart.

Fourth, my Neuroscience major. Taking this class and completing my neuroscience major has allowed me to also learn so many skills. Taking biochemistry, neurobiology, and neurochemistry consecutively has deepened my admiration for neuroscience and research. This year, I read more research papers than I have ever read in all my time in school, and this was due to the research projects and classes I found myself . I struggled at first because I had not learnt the skill to navigate such literature. However, I understood that this was an important skill to learn, so I took up the challenge. Looking back now at the end of the semester, I am no longer scared of this skill I once lacked. I have been able to improve to the level of having confidence in my ability to navigate difficult academic literature. I am particularly grateful for this class because I felt encouraged to face this challenge when I encountered it initially. This is one skill I will definitely highlight on my resume from this semester.

Fifth, friends. Finding my community here at Concordia gave me a sense of belonging, especially when I struggled with different situations. I am grateful for the people who always made me realize my flaws and were kind to direct me in my areas of weakness. I am also grateful for those who congratulated me on my wins, even when I felt that they were negligible. Most times, when I felt alone, having those who had my best interest at heart reminded me of my strengths. More specifically, I am grateful for all the

I very excited to take these skills to the next journey. For me, this is only the beginning of a new transition. I wish to utilize the skills I have built to progress in my journey and career. Thank you Concordia!

Neurochemistry has been one of my favorite classes that I have taken in my college career. Although this is technically a science class, it covers the full spectrum of liberal learning that ultimately provides students with a strong foundation to excel in many different environments. This class is based around neurochemical signaling pathways, which I truly found fascinating. Although there are many methods used to understand how the body works and what goes wrong in different diseases, using signaling as a mode of understanding these processes allows for both very broad and also very specific interpretations.

This class has showed me that it is important to look at problems from diverse perspectives in order to reach the underlying issues. It is important to look at issues from a top-down approach as well as a bottom-up approach. Looking at behaviors from the molecular signaling level will allow for a particular understanding, and looking at the same topic from a global or societal perspective may lead you to completely different ideas. Value comes from looking at an issue from both perspectives to find tangible, actionable steps that can produce microscopic and macroscopic benefits.

I truly enjoyed hearing all of my classmates’ opinions and perspectives on all of the topics that were covered. Hearing other people’s ideas in such an in-depth way really deepened my understanding of our class topics. The discussions in this class provided an environment where diverse perspective can be shared that can help us have deeper understanding of why these topics are important. The perspectives of my classmates deepened my scientific knowledge as well as my social, ethical, and cultural knowledge.

While it may seem that covering such a wide scope of information would provide a disjointed education, I completely disagree. In my opinion, taking a topic and analyzing its microscopic and macroscopic implications really helps establish the importance of liberal education. When students are able to realize that chemistry is valuable outside of the lab, then they can integrate new modes of thinking that would not be possible otherwise. Integrating social, ethical, and cultural considerations into scientific discussion can provide new perspectives and allow for more relevant approaches to science.

Although I have only been at Concordia for a short time compared to my classmates, this class integrates many of the competencies that I have previously learned. This class provides a succinct format for understanding some of the tiniest details of life as well as some of life’s most complex problems. We cover many complex topics ranging from which ions are being moved through the membrane of a neuron following a concussion to how the public education system can be improved for diverse populations. These topics allow us to utilize a wide range of skills such as reading scientific literature, writing about complex topics, explaining our perspectives and opinions, and looking at concepts from different perspectives.

As a future medical professional, the skill of taking complex scientific and medical topics and breaking them down into understandable bits of information is extremely valuable to me. This is not only valuable for my own education and understanding of topics, but also for my ability to explain diseases and treatments to my patients. Over this semester I believe that my ability to take in, simplify, and explain complex neurochemical topics has greatly improved.

Even though I am not yet graduating, I know that the concepts we covered in this class will benefit my future career regardless of what field I end up in. This class has showed me that it is important to look at problems from diverse perspectives in order to get to the underlying issues. It is important to look at issues from a top-down approach as well as a bottom-up approach. Looking at behaviors from the molecular signaling level will allow for a particular understanding, and looking at the same topic from a global or societal perspective may lead you to completely different ideas. Value comes from looking at an issue from both perspectives to find tangible, actionable steps that can produce microscopic and macroscopic benefits.