Cobbers on the Brain

What are Endocannabinoids

Endocannabinoids (eCBs) are naturally produced in the body and are lipid-based neurotransmitters. The primary endocannabinoids are arachidonoyl ethionamides (AEA) and 2-archidonoyl glycerol (2-AG) which are agonists to CB1 and CB2 but bind to both receptors. However, CB1 has a higher binding affinity than CB2. eCBs are produced as the body needs them by an increase in intracellular calcium and are degraded through fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). FAAH breaks down AEA and MAGL breaks down 2-AG. The benefits of the endocannabinoid system are that it aids in mood, pain, perception, and learning and memory.

CB1 and CB2 Receptors

CB1 receptors are found primarily in the central nervous system (CNS) and CB2 receptors are primarily in the peripheral nervous system (PNS). CB1 receptor accounts for being the most abundant GPCR in the CNS but is also located on peripheral nerve terminals. Besides binding AEA and 2-AG THC, the main ingredient in cannabis sativa (marijuana), binds at CB1. CB2 receptors can be found in the CNS but are mainly located in cells and tissues of the immune system. CB2 receptors in the CNS are localized to microglia and modulate inhibitory plasticity. Additionally, CB1 and CB2 receptors operate independently from each other.

Receptor Activation

Following activation of CB1 there is a rapid decrease in the levels of cAMP via adenylate cyclase inhibition. This decrease occurs through activation resulting in potassium channel conductance and a decrease in calcium voltage operated channels. Ultimately resulting in a decrease in neurotransmitter release. However, prolonged exposure can result in tolerance and a decrease in the ability of the receptors to activate the endocannabinoid pathway. AEA and 2-AG can bind and activate CB receptors but so can THC and CBD from marijuana.

AEA, 2-AG, THC, and CBD are the only agonists that can bind to CB receptors. However, there are ways to enhance endocannabinoid levels and receptor activation. Both dark chocolate and black truffles contain anandamide (naturally produced endocannabinoid), caffeine, olive oil, exercise, and omega-3 fatty acids upregulate CB receptors. Lastly, cold exposure increases endocannabinoid levels and flavonoids found in tea and wine inhibit the breakdown of endocannabinoids.

Endocannabinoids and Pain

The activation of the endocannabinoid system is associated with pain reduction. However, natural endocannabinoids may not be able to provide the level of activation required of the endocannabinoid system which is when cannabinoids of THC and CBD are introduced. Research has linked cannabis to control and manage pain associated with Alzheimer’s disease (AD), Huntington’s disease (HD), and multiple sclerosis (MS). In MS eCB system activation reduced pain and spasms and provided neuroprotective and anti-inflammatory effects. In HD CB1 receptor activation is reduced, resulting in reduced motor performance. Therefore, enhanced activation of remaining CB1 receptors may help the degradation of the receptors. In AD CB receptor activation is thought to produce a neuroprotective effect and protect individuals against amyloid beta plaque toxicity and reduced tau phosphorylation.

Conclusion

Endocannabinoids are naturally produced in the body and are agonist to CB1 and CB2 receptors, as are phytocannabinoids, THC and CBD. The activation of the endocannabinoid system has been linked to pain reduction, mood stabilization, and memory and learning. Research has begun investigating the therapeutic effects of endocannabinoids on diseases such as HD, MS, and AD.

References

[1] 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

[2] De Pietro, MaryAnn, CRT (2021). What to know about endocannabinoids and the endocannabinoid system. Medical News Today. https://www.medicalnewstoday.com/articles/endocannabinoid

[3] Fallis, Jordan (2023). 26 powerful ways to boost your endocannabinoid system. Optimal Living Dynamics. https://www.optimallivingdynamics.com/blog/how-to-stimulate-and-support-your-endocannabinoid-system#:~:text=Medium%20and%20high%2Dintensity%20exercise,68%2C%2072%2C%2074)

Introduction

I enjoyed this class because it gave me a chance to blend what I learned from my neuroscience classes with what I learned from my psychology classes. This class focused on the pathology of mental disorders, but I found that my psychology background helped me better understand the whole picture. Both aspects are important because the biology of the brain determines the behavior, but your behavior can also affect the biology of the brain, and both need to be addressed when treating mental disorders. My understanding of mental disorders helped me to connect more with the pathology behind them.

I also think that my psychology background gave me a unique perspective on some of the topics that we covered during our Friday discussion days. I think it’s really easy for the sciences to forget about the humans behind the disorders that are being studied. While psychology is not immune to this, I think neuroscience is at a greater risk because it is so focused on pathology and often only used animal models in its research. The fact that I was taking Abnormal Psychology at the same time as this class made me a lot more aware of how I talk about mental disorders, like when we discussed depression and psychopathy, and how these discussions weren’t always the most sensitive. I know I had to work really hard to keep my comments both scientifically accurate and empathetic at the same time and my psychology background helped me with this.

What Kinds of Learning Occurred for You During this Semester?

My learning for this semester wasn’t so much focused on memorizing information as it was on learning how to read scientific publications and present my findings. Yes, I learned about a lot of signaling pathways that I was unfamiliar with, and I am at least generally aware of how they work now. But there was a lot more time spent on practicing how to read scientific articles, because they’re not the type of writing that you can just pick up, read once, and expect to understand what is going on. You have to take notes, you have to highlight the important parts, you have to identify what you don’t understand and then research those parts. I think that was the most important skill that I learned. The importance of figuring out what you don’t understand and then learning how to teach yourself about it. This was something that I had never done before because I assumed I was supposed to understand everything on the first try. I’m glad that I learned this skill though because it made the publications a lot easier to understand and a lot more enjoyable by proxy.

If You Were to Highlight on Your Resume a Skill or Competency that You Improved this Semester, What Would You be Sure to Include?

This class will be very useful for my future career plans of going into research. The focus that this class placed on understanding how to read scientific articles will come in handy since a lot of research is reviewing past literature. I also found the focus on communicating our findings to the general public to be very useful. When you’re taking a lot of STEM classes and you are friends with mostly other STEM majors, it can be really easy to forget that not everyone understands the lingo that you use. I found the weekly blog posts to be a useful exercise to help me get out of the habit of using those complicated words, because every time I used a niche word, I had to explain what it meant and that got tedious. These blog posts also helped me think more about the way that I present information. Is it entertaining? Is it easy to follow? Am I putting people to sleep with this long paragraph? These are all questions that I started to ask myself when writing my blog posts, and I am hoping to carry that habit with me when writing my own scientific articles.

I’m really glad that this class focused so much on becoming better writers. It’s something that is often overlooked during our science classes, which explains why research articles can be so difficult to read. Hopefully I can be one of the good writers in the scientific community and people will actually like reading my publications.

Conclusion

This class was both really challenging but also fun. The homework took a really long time, but I feel the skills that I gained from doing the homework made it worth the time. It wasn’t just busy work, it taught me how to read and understand scientific articles. It also taught me how to share research with the general public in a more digestible manner. This is a skill that more science students need to be taught because currently academic writing in the sciences is atrocious. I think these skills will be extremely valuable to me when I graduate because I’m planning on going into research, and that field requires a lot of reading scientific literature and sharing my findings with the public. I’ll be sure to put this class on my CV to highlight the skills that I gained.

Concordia and me

In high school, I never thought I would pick Concordia College for the next four years of my education. It was really the people here that drew me into picking the school. I remember visiting schools across the nation and thinking I do not want to stay this close to home, so I don’t need to look at Concordia. I don’t know how or why I did look into Concordia, but the community caught my attention. I got the opportunity to talk to a professor and it really struck me that those small classrooms, close connections to my professor and peers are what I wanted. Throughout my years here now, I have really seen myself learn and grow through not only the curriculum, but also the community within the science department and outside of it too.

Concordia has five goals set in place for the liberal learning experience here on campus. The first is to instill a love for learning. There were definitely classes that I thought were brutal and I won’t lie, it was stressful keeping up sometimes. At the end of the day, however, I was always beyond impressed by how much I found myself learning about so many different topics. Neuroscience was just a major that I thought would be fun to learn about, but I can say all my neuroscience classes were by far my most favorite and I loved learning in every single one of them. I ended up adding a Biology major because why not learn more in more areas!?

The second goal is to develop foundational skills and transferable intellectual capacities. All of my classes have always been so hands on and discussion based where I feel like I gained skills that would be applicable to real life. The labs especially taught me a large varieties of skills including teamwork, problem solving, scientific reasoning, etc. My environmental and global studies classes were also important I thought to me because they gave me more knowledge of real world issues that I otherwise may have been ignorant about.

The third goal to develop an understanding of disciplinary, interdisciplinary, and intercultural perspectives and their connections. While I love my major specific classes, I really liked the well rounded aspect of the liberal learning here at Concordia that allows me to take classes of different subjects as well. I feel like I know so much more about the world and everything out there. My Spanish and inquiry classes especially we got to go out in the communities and talk to people and that was very cool! In my inquiry, we got to go to the New American Consortium and work with people of different cultural backgrounds, which was one of my favorite experiences right off the bat coming into college. These experiences in such classes I thought also really pushed for the fifth goal which is to encourage responsible participation in the world. The clubs and activities also added to my growth in these areas, especially when I was on the DEIC executive committee board. That role was especially fun because I got to really learn about different culture’s celebrations in order to recreate them here on campus. I think this also helped with the fourth goal: Cultivate an examined cultural, ethical, physical and spiritual self-understanding. I think I learned more about myself and the diverse group of people around me through my experiences at Concordia.

This semester and me

This semester was one of my favorites because I think I learned about so many diverse subjects in my classes. Neurochemistry was one of my favorites in my entire college career because of the design of the class being so discussion heavy. In this class I felt like I could use prior knowledge from many of my classes to analyze real life health conditions affecting people in the world. Once we problem solved understanding research articles and the brain pathways causing a variety of illnesses, we could dig deeper into the subject. It was not always just straight science. The open ideas structure really allowed us to learn about so much more like environmental impacts on health or psychological or food or the government and societal stigma. The topics were endless and I loved that lack of restriction in class.

The amount of information and just analyzing skills I have gained from reading, understanding, and discussing so many articles will for sure help me in my career path to becoming a doctor. I think any career, including the ones in healthcare, need skills that involve investigating what is wrong and how it can be fixed. We did this a lot with so many different health conditions throughout the semester. Knowing how these health conditions are formed was really interesting and will be impactful in the future when I may have patients who have many of these.

The discussion-based format of Neurochemistry also played such a huge role in the friendships I have strengthened after the class. Instead of just sitting next to strangers for a semester and listening to lectures, we got to talk to each other and hear so many perspectives of people with so many different backgrounds. We even started hanging out outside of class, which we had never done before this class (as seen in the top featured picture).

Artstract by Dhruvika Patel

What are Cognitive Impairments?

Cognitive impairments are issues that interfere with a person’s ability to think, learn, remember, use proper judgement, and make thought out decisions. There are many signs that can be found in those that might have an impairment, including memory loss, difficulty with concentration, task completion, remembering, following instructions, and solving issues. Due to the wide variety of impacts that can occur, it makes sense that there would be detrimental effects not only on the person, but also their family’s finances. These finances can be a result of increased costs for education, healthcare, and personal daily care. Furthermore, we can’t ignore the emotional burden that also falls upon the family to take on an often-lifelong responsibility. However, their story is not destined to be hopeless forever. There are therapies that can occur to better cognitive abilities along with further research that looks at more possibilities to train the brain through enrichments.

Epigenetics and Enrichment

Epigenetic mechanisms regulate transcription and gene expression. Recent findings suggest that epigenetic processes can be changed through environmental and social rearing conditions. An epigenetic modification is BDNF increase in the hippocampus exposed to environmental enrichment. Environmental enrichment is comprised of 3 domains: increased physical activity, increased social groupings, and increased opportunities for exploration. There are complications to enrichment studies; however, these include having a control group with no confounding variables and manipulating the genome in mutant mouse models.

Brain Mechanisms

Cognitive function depends mainly on neuronal activity and engagement of synaptic proteins and signaling cascades to promote the establishment and strengthening of synaptic contacts. Positive modulators of AMPA receptor have positive effects on learning and memory in rodents. Ampakines are a class of positive allosteric AMPA receptor modulators that work with learning and memory but also promote BDNF expression and protect the brain from neurodegeneration. BDNF is important for neuronal survival, differentiation in the brain, and LTP and learning. Furthermore, Ras-ERK signaling activation is needed for LTP and long-term memories, so germline mutations can be responsible for a variety of neurodevelopmental disorders. BDNF is one thing that is engaged in this RAS-ERK pathway and is important in LTP.

BDNF

Brain-derived neurotrophic factor is like the fertilizer of the brain. It is found in the CNS, gut, and other tissues that play an important role in neuronal survival and growth, is a NT modulator, and helps with neuronal plasticity, which is important for learning and memory. BDNF is synthesized in the brain and is released in response to neuronal activity. It binds to specific receptors on the surface of neurons, promoting their survival and growth. Therefore, sufficient BDNF is very important in cognitive abilities. Reduced levels of BDNF are associated with impaired cognitive function and increased risk of cognitive decline and neurodegenerative diseases. Conversely, increased levels of BDNF have been linked to improved cognitive function and better outcomes in conditions such as Alzheimer’s disease and depression. Several studies have suggested that certain nootropics, such as caffeine, creatine, and omega-3 fatty acids, may increase BDNF levels in the brain.

Conclusion

Cognitive impairments impact a fairly large number of people in the world; it not only affects the person, but also their family. BDNF is one area that has been looked at due to its connection with neuronal plasticity. There are natural nootropics that can be taken to enhance such brain function along with environmental enrichment.

Citations

Faiz, M. (2022, February 11). What is BDNF and Why it’s Important for Mental Health? Personalized Prescribing. https://personalizedprescribing.com/blogs/news/what-is-bdnf-and-why-its-important-for-mental-health

Jin, Y., Sun, L. H., Yang, W., Cui, R. J., & Xu, S. B. (n.d.). The role of BDNF in the neuroimmune axis regulation of mood disorders. Frontiers in Neurology, 10. https://doi.org/10.3389/fneur.2019.00515

Morè, L., Lauterborn, J. C., Papaleo, F., & Brambilla, R. (2020). Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 110, 28–45. https://doi.org/10.1016/j.neubiorev.2019.02.003

NCI dictionary of cancer terms. (n.d.). National Cancer Institute. Retrieved May 4, 2023, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cognitive-impairment

I chose Concordia mainly because it was a smaller campus that was a good distance from home. Originally from St. Cloud, I didn’t want to stay in the area after high school despite the many good schools that are around there. I had never been to Fargo-Moorhead before, and to be honest I’m not sure how I first found out about Concordia. During high school I was always interested in chemistry and the brain, and hearing that they had a strong chemistry department as well as a neuroscience major it soon became a top choice for me. I wanted to go into pharmaceuticals and drug development and research, so chemistry seemed like the best fit.

I came in as a freshman in 2019 as a chemistry major with a neurochemistry concentration. I loved the classes I was taking and felt it was the right fit for me. However as well all know that got totally ruined spring of 2020, and my college experience completely changed. I am very much an in person learner, and trying to take organic chemistry my sophomore year half online, while dealing with the mess and personal stress from that year, made me rethink my choices. I was not doing well in my classes, and through lots of conversations with my professors, friends, and even my therapist, I decided to drop my chemistry major and switch to a neuroscience major.

Don’t get me wrong, I love neuroscience and I’ll never regret the decision to switch. But one important thing about me is that I do not like biology. Plants and cells are the bane of my existence, and going into neuroscience as a career the main options were biology based or psychology based. And neither of those really spoke to me. Close to the end of the fall semester of what should have been my senior year, I had a conversation with some friends who had taken organic chemistry in the summer, and how much they loved it. I went home thinking about how I could love that class, and how it would open the door to be able to focus on chemistry again. Two days later I decided to do a Flex Year and stay at Concordia to complete a chemistry major.

I then went on to take physical chemistry, abnormal psychology, inorganic chemistry, and neurochemistry. And I finally felt like what I was learning and what my path was turning out to be what I wanted. Neurochemistry has been one of my favorite classes that I’ve taken, and it easily fulfills all the goals for learning that Concordia has. Most notably are these two:

1. Instill a Love for Learning
   • This class really solidified that I want to go into drug development, almost every signaling pathway we talked about and neural system had an application into pharmacologic treatment. I found myself excited to read the papers for this class, and to go to discussion days on Fridays to see what ideas my classmates have. I’ve recommended this class to so many people because of how enjoyable I found it.
2. Encourage Responsible Participation in the World
   • During our weekly papers and discussion topics we often talked about illnesses and diseases that are seriously detrimental to people. A lot of these topics made me realize that the work I do in the future could potentially impact tons of people. It made me excited about the field I want to go into.

This class will always have a special place in my heart.

Concordia has shown me and taught me so much more than I could ever imagine. I can’t put into words how grateful I am to all the people who has led me through the last four years of my life. All I have to say is don’t let it go by so fast, and trust me it really does. Everyone always says that, but no one believes that it’s true until it all happens.  Get involved as much as you can, make as many friends as you can, make great memories, and make the best out of your college experience. Live your best life, I know I sure did!

My College Journey

I started off my freshman year at Concordia as a Biology major, hoping to take the Premed route, but that quickly changed after taking a few biology and chemistry classes. I was always interested in how the body worked and why it did the things that it did, but college classes are hard. I was minoring in psychology as the time, as well. About halfway through my sophomore year, I switched to a double major in neuroscience and psychology. I’ve been enjoying this much more, mostly because there’s less biology and chemistry involved. Don’t get me wrong, there’s still a bit of the two topics but nothing I can’t handle. I had never taken a chemistry class before coming to college, and I really struggled through the few chemistry courses I did take. Neurochemistry has been, by far, my favorite chemistry course. The main reason is because of how the class is structured. I loved that every Monday, Wednesday, and Friday there was a set schedule. For Monday class I had to read an article, complete a worksheet based on that article, and discuss in class on Monday. For Wednesday, we would each be assigned a topic and would have to research and report on the topic to the class. And on Friday, we would split up into two different groups and students would lead a discussion. I have never been in a class that was structured the way Neurochemistry with Dr. Mach is. I was worried that I wouldn’t understand this class, but I did, and I enjoyed the entire semester of it.

 

Why Liberal Arts?

A liberal arts college has a goal to help students learn about everything and gain knowledge in many different places. I learned this through taking many different required and elective courses. As a student at Concordia, we are required to take two religion courses, PEAK courses, and a language course. At first, I wasn’t a fan of taking so many required courses that I thought wouldn’t have anything to do with my future. But I’ve enjoyed being emersed in the many different courses that Concordia has provided. If I were to highlight something on my resume that I have improved upon during my time at Concordia, I would be sure to mention that I have learned how to talk with others who I don’t agree with. Attending classes that were required to graduate introduced me to a lot of people who I would never have met. I enjoyed chatting with those who I disagreed with because it opens so many different possibilities.

What Now?

The last four years have gone by faster I could have imagined, but I enjoyed every minute of it. Being involved in college athletics is hard to balance with schoolwork but that was one of my favorite parts about these four years. I will be back for an extra semester, but that doesn’t mean I won’t miss what the past four years have provided for me. I want to use all the skills that Concordia has provided to me in the future. I want to be able to communicate effectively with others, share my thoughts, and fight for what I believe in. I hope to go into the medical field, work with children, and do something that has to do with neuroscience and psychology combined. I know Concordia has prepared me for whatever I decide to do, and I sure am going to miss all the connections and memories I made. #RollCobbs