Cobbers on the Brain

We’ve spoken quite a bit about the impacts that amyloid plaque can have on the anatomy of our brains, and subsequently how those changes in anatomy can have negative effects on our cognitive function. But in case you forgot I will provide a brief overview. Plaques accumulate over time naturally, however, in Alzheimer’s our brain fails to keep up with the demand for clearance and is therefore overwhelmed by the buildup of these plaques. The abnormal levels of these plaques clump together and are found positioned between neurons, ultimately disrupting cellular function as shown below (U.S. Department of Health and Human Services). 

Consider for a moment that we could simply remove these plaques, it may not solve our problem entirely but perhaps it could lead to a decrease in negative symptoms momentarily. Lucky for us the advancement of technology has provided new techniques to not only decrease amyloid plaque formation initially, but to potentially remove it from an area entirely after is has begun to accumulate. 

It might be helpful to first provide some background information that is required to understand the topic. Embedded within an amyloid plaque lies a protein called APOE. APOE is located near the center of the amyloid-APOE complex and is accessible from the exterior given the right circumstances. These complexes come together with AB Fibrils, proteins that are initially soluble but become insoluble after their assembly is altered, this combination is what forms the amyloid plaques that we are so used to talking about. You can see this without my poor explanation in the figure shown below.

Changes in APOE proteins are thought to be one of the largest risk factors for Alzheimer’s, different unnatural changes to the protein can lead to differing severities of the disease. The figure below demonstrates the negative side effects that can come from the unnatural variations of APOE. 

Researchers at Washington University recently discovered antibodies that can target and initiate removal of plaques from the brain by directly binding to the APOE domains. By doing this the antibodies effectively flag the compound for degradation by the local immune system. Although it is meant to be a humorous take on the immune systems response to APOE, the picture that I altered may help you remember this point. 

When these immune cells target the APOE, scientists discovered that the immune cells would also carry away the connected amyloid plaque that had formed around the APOE. In this situation you can think of the APOE-plaque complex as the metaphorical saying “throwing the baby out with the bathwater,” except in this case it’s a positive.

It should be noted however, that there is a caveat to this claim relating to the removal of plaques via antibody binding. Scientists believe that using antibodies may only be effective during the early stages of amyloid plaque build-up. The scientists from Washington noted that if too much plaque is present, that the addition of antibodies might not be enough to counteract the inevitable disease that is Alzheimer’s.

“Okay,” you might say, “but surely APOE has other important roles in the body, degrading all of it would be bad.” And indeed you would be right, APOE does have other important roles in the body such as “the transfer of cholesterol and phospholipid between cells” (Liao et al, 2017). Luckily however, researchers found an antibody that only affects the APOE in the brain and not throughout the rest of the body. Initially the researchers were stumped as to why the antibody (antibody HAE-4) only affected the APOE in the brain. But of course, someone else had done their research for them, it turns out that there are three different naturally occurring isoforms of APOE. Different isoforms are present depending on the region of the body, the brain having its own individual isoform entirely (from what I gathered from the article). This difference allows antibodies, and therefore researchers, to target the brain’s APOE without worrying about damaging the subject. Because of this discrepancy, researchers can potentially use antibody technology to prevent Alzheimer’s disease in the future.

Sources

Liao, F., Yoon, H., & Kim, J. (2017, February). Apolipoprotein E metabolism and functions in brain and its role in Alzheimer’s disease. Current opinion in lipidology. Retrieved September 27, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5213812/.   

ScienceDaily. (2018, March 26). Antibody removes alzheimer’s plaques, in mice. ScienceDaily. Retrieved September 27, 2021, from https://www.sciencedaily.com/releases/2018/03/180326161000.htm.  

U.S. Department of Health and Human Services. (n.d.). What happens to the brain in alzheimer’s disease? National Institute on Aging. Retrieved September 27, 2021, from https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease.  

Many of the skills I’ve learned throughout college are skills I thought I already knew. Courses such as Christianity and Religious Diversity, Social Psychology, Organismal Biology and Philosophy of Art, among many others, have taught me how to think critically about different problems and the world itself. Our Neurochemistry course has undoubtedly improved my critical thinking skills as well- group discussions centered around research implications every week and exams that required synthesizing ideas instead of memorizing information have given me invaluable practice for processing and working with concepts in the moment. The biggest thing I’ve learned from this course, however, is how to learn itself. As a byproduct, this has exponentially increased my confidence in the scientific field.

At the beginning of the course, I relied on the learning strategies that have always been enough in the past, and quickly realized that I would need to adopt new methods to succeed. Usually, I would copy down notes from lecture, read the textbook, and go through it all over and over before an exam. This had worked great for me previously, but since there weren’t any true lectures in the course, this process need to be replaced with utilizing new resources. These included information that my classmates had shared and learning how to conduct my own background research.

Neurochemistry was also the first time that I was pushed to understand research articles from top to bottom; this was a learning curve for me because I was used to just skimming the introduction and discussion of articles, but I was surprised by how much I was able to comprehend on my own by the end of course. While it definitely required more time and effort, the structure of this course taught me how to better integrate information into my foundation of knowledge, instead of passively absorbing content. More specific skills that I’ve also taken away from the course include pulling information together from various sources and communicating it in an effective way to different audiences. 

As my understanding and appreciation for neuroscience has grown since I began my studies in the field last year, I’ve slowly begun to see themes in the inner workings of the brain. Through investigating a diverse mix of neurological conditions/diseases and the cellular processes that underlie them, our neurochemistry course in particular has helped me piece together some overarching patterns. Interestingly, one of these themes is relevant on a larger scale, including life itself: balance. 

The Theme of Balance Throughout Different Neurological Disorders

On a biological level, this idea of balance is conceptualized as homeostasis, and as I learned in this course, loss of homeostasis can lead to many neurological disorders. The functioning of our brain is very tightly controlled, with many feedback loops and mechanisms for auto-regulation. An example that demonstrates how disruption of excitation/inhibition balance can contribute to pathophysiology – often meaning disruptions in glutamate or GABA signaling, the main excitatory and inhibitory neurotransmitters in the brain – is anxiety.

In general, overabundance of glutamate and low levels of GABA can lead to an anxiety response, with many underlying mechanisms and areas involved that are responsible for this happening. As I learned while conducting research for the course, one of these mechanisms involve GABAergic signaling in the amygdala; these circuits normally work to inhibit the amygdala’s interaction with stress, but chronic stress may cause the networks to reduce, lowering amount of inhibition and increasing anxiety as a result. Overexpression of glutamate is thought to contribute to many other disorders as well, such as autism spectrum disorder and schizophrenia, while underexpression has been indicated in obsessive-compulsive disorder. Another type of imbalance between orexigenic and anorexigenic peptides can promote metabolic syndrome, essentially increasing food intake while decreasing energy expenditure. 

In attempt to resolve certain disruptions to homeostasis, the brain can implement compensatory mechanisms that counteract the disruption. Behavioral tolerance after consistent drug use is an example of this; through dopamine-mediated pairing of stimuli, the brain implements effects opposite of the drug when exposed to the associated cue, and this process can contribute to drug overdose and relapse. Compensatory mechanisms can even be seen after Traumatic Brain Injury, where ionic pumps shift into overdrive and cause hyperglycolysis in an effort to restore ionic and cellular homeostasis that were disturbed from the initial biomechanical blow to the head. 

While these connections may seem a bit out of context as a whole, balance has always been a significant challenge in my own life, and as a result it has become a major value. More than just juggling everyday priorities, I’m still figuring out how to manage my own levels of excitation and inhibition. Without constant and consistent effort, I quickly fall into patterns that only harm myself and perpetuate a cycle of dysregulation that can be extremely difficult to break out of. I would guess that in some way or another, many people can relate to this feeling of being out of control when it comes to regulating themselves or their lives. 

Of course, the etiology of these disorders are more complex than ‘imbalances in the brain’, as the common rhetoric often goes, but understanding that they can stem from impairments to our brain’s mechanisms for maintaining balance can ultimately help remove stigma and blame from the individual. Especially for conditions such as metabolic disorder, where many people have essentially been told that their struggles are completely due to their actions, learning the physiological reasons for what they are dealing with might actually allow them to find ways forward through education and empowerment.

Considering that many mental health and neurological disorders involve an aspect of difficulties with self-regulation on a behavioral level as well as a physiological one, treatment plans may often benefit from a multi-dimensional approach. To me, this stresses the importance of integrating the psychological and neurological fields as much as possible; as someone who is interested in a mental-health related career, I intend to do just that, equipped with the skills I’ve gained from our Neurochemistry course. 

If you are anything like me, the time around finals is when your immune system goes extinct. This happens every year during mid December for me. Finals start approaching and stress levels begin to rise. I have tried a variety of different things to do to avoid getting sick, but nothing has seemed to work. A recent article that we discussed in class offered a potential therapy or “treatment” to possibly help prevent this. This therapy is music.

In the article, music is talked about like it’s a special drug. The reading discussed how music helps lower stress levels and improve immune system markers. Studies showed cortisol levels before and after the listening of music. The results showed a significant decrease in cortisol. This lowers stress as cortisol represents stress levels. One musical aspect researchers looked at was group drumming. The drumming allowed for participants to engage in a rhythm based beat together. Lymphocyte numbers increased as well as immune system markers such as IL-6 during this engagement. The article also referenced positive feedback after participating in group singing. During group singing, s-Iga concentrations rose by a drastic amount.

Is it Really Music?

One big question that was common throughout the whole class was the actual power of music. In many of these studies, there were other contributing factors that may have lead to the positive feedback. Examples of the singing and group drumming are the social aspects of those. While drumming in a group or singing with your choir, you are surrounded by people who I would assume you like to be around. So we question whether it’s the actual music or the environment. In many of the individual research that our class performs, many of them hinted that music does in fact improve your stress levels by a large margin over everything else. Me being the sports junky I am would assume that playing a game of baseball would provide the same benefits as an individual singing in the choir. This however has been overturned and said that music is still much more effective when it comes to reducing stress.

Still a Right Fit for You

A large amount of these studies have to deal with classical music. Studies often involve singing or listening to classical music. For many of you, classical music may not be your type. Although more research needs to be done, research still hints at it doesn’t matter whether or not you like the music. Engaging in classical music will still perhaps benefit you whether you like the genre or not. 

With finals time approaching, try something new this year. If you struggle with stress and see a decline in your immune system then you should try putting some music on. Through these studies, you can see the positive impact either listening or singing to music can play on your body. 

Registration for the fall of 2021 began during end of spring semester in 2020. To fulfill my PEAK requirements at Concordia, I decided I would sign up for Neurochemistry. As a chemistry major, I really was not looking forward to the class if I am being honest. I did not know much about the brain and felt as if I would be behind throughout the whole semester. When the semester was about to begin, Concordia sent out a notice telling students that they did not have to do two PEAKS. I had already had my one PEAK credit, so dropping neurochemistry crossed my mind. I kept going back and forth and finally felt the motivation to try something new and stay enrolled. When classes began, I was behind. This however gave me opportunities to learn new things. We first started class lectures by reading papers on certain signaling pathways and discussing anatomy of the brain. I started to become interested when I realized how real these pathways were. The interest in the course only became larger when we started to discuss diseases that could possibly be associated with the brain.

Throughout my time as a Neurochemistry student, I started to gradually learn more each time. I looked forward to class and hearing what others had to bring to the table. There were different perspectives and opinions all over the room, but the class allowed us to share our differences in a nonjudgmental way. One cool part about all the information the class provided was that I took that knowledge with me and discussed it further with my roommates. Unlike many other classes, neurochemistry built a platform that could take with me and easily show others what I learned.

Following Concordia’s goals, I was also able to learn more about different cultures. For example, we might have wondered why a certain country has more cases of autism than another country. I have always thought of neuro disorders as a worldwide diagnosis, but the class allowed us to see the cultural differences. Learning these culture differences was new to me and more information I could further share with others. Sharing with others, as you might tell, was a common theme in the class. Dr. Mach did a great job of creating an environment where everyone was engaged. Being able to share our information to others was awesome. This also is what encourages to further our engagement and continue to share with the world.

The skills that were learned throughout the course were all new to me. Obviously, I knew some of the chemistry, but I had never applied it like this course taught me to do. All my learning was new information which was strange to me. I say strange as in a good way. All my life, I have been taking courses that I at least have some knowledge on. For example, in Calculus 2, everyone is around the same in terms of known information. The first couple of chapters are parts of Calculus 1 that you had already learned. In Neurochemistry, it was always something new. This new information was then able to be shared on our class blog. The blog allowed us to share what we learned from each of our papers. Not only was this fun to do, but it allowed me to transfer those skills into the real world. As a potential future pharmacist, I will have to provide information that I have studied to customers. This in a way relates to the blogs. I studied and received information and then shared the blogs for the whole world to see.

I must thank Concordia for providing a liberal arts education because if it weren’t for the initial PEAK requirements, I would have never thought about taking this class. This is something that one really does not understand until they go through the liberal arts education. Freshman year we see a lot of students upset about all the extra “dumb” courses they have to take. I will not lie; I was one of those students. If senior Toby Sayles could say anything to freshman Toby, I would call him the dumb one. The liberal arts curriculum has allowed me to branch off into a variety of different courses. All of the courses that were considered “extra” were my most memorable courses. The skills and information gained from the two PEAK courses I took will surpass any of the skills I take from other courses. I feel all students should experience a liberal arts education in the pure fact that it might make the world a better place.

Lastly, if I were to put a skill on my resume that has upgraded the most from Neurochemistry it would be my listening skills. By active listening, I was able to gain more information than ever have before. Although it was not always easy to listen to different opinions, I learned that by doing so I could better understand my own. Neurochemistry has allowed me an opportunity to better myself as an individual and a student and I will forever be grateful for that.