Cobbers on the Brain

Sometimes we like to make fun of liberal arts degrees.  I may not understand my tax forms, but at least I know about quantum tunnelling!  Those kinds of comments happen often.  Learning about seemingly random things you never thought you were signing up for is tedious at times, but when you step back and look at what four years has done, you start to appreciate it.
During senior year, students take a capstone course as the culmination of their liberal arts education.  The courses are designed to blend disparate fields of study and bring them together to deepen students’ knowledge about a topic.  Capstone courses also involve cultural awareness and involvement in the local community.  At Concordia, topics of capstone courses include world musics, dangerous literature, and the biochemistry of cancer.  I took neurochemistry for my capstone course.  Don’t worry, it was actually a lot more fun than I expected.  
What do capstone courses have that others don’t?  That became clear in our weekly group discussions.  We would break into small groups and discuss aspects of the disease/ issue/ chemical pathway of the week.  During our week on schizophrenia, a student brought up an idea from an Indian religions class.  A person with schizophrenia living in India might not be avoided as a dangerous anomaly.  Instead they might be treated with respectful distance or even valued as someone with a gift.  Maybe the way we shun people with mental illness in America contributes to poorer outcomes for patients.  In a normal neurochemistry class, no one would have ever raised that question.  
When our different skills came together, our overall understanding grew tremendously.  As we tried to understand a research article on addiction, students from different fields had different perspectives to give.  Neuroscience majors explained the mechanisms of reward and long-term changes in the dopamine neurons of the striatum.  Psychology majors told us about how the reward pathway works on a larger scale with classical conditioning and state dependent memory.  Pre-med students understood that many addictions begin with prescription narcotics, and that the opioid epidemic is driven by more than individual brains, but by systemic, bureaucratic problems.  With many people adding their own experiences to the pile, everyone developed a broader knowledge of the issue.  
The ultimate aim, of course, is coming closer to fixing intractable diseases– of brains and of society.  A sweeping, entrenched epidemic like we see with opioids can not be solved using only neuroscientists.  Medications need to be prescribed by vigilant doctors and accompanied by therapy from perceptive counselors.  We will need meticulous statisticians to help to manage the health of millions of people.  Only social workers are able to help the families of addicts, and sometimes to heal fully you need a musician or a comedian thrown in for good measure.  Before I took my capstone course I knew that teamwork would be necessary, but the course showed me how to make that teamwork happen, and how powerful a synthesis of minds can be.  

The neurochemistry capstone is unlike any science class I have taken at Concordia. While the background of chemistry, biology, and neuroscience is helpful, it was learning how everything relates that was so integral to the articles. With each article came a new discussion, direction, and potential solutions to the many problems. It was great to have students with different backgrounds in the class which really helped our discussions throughout the weeks. We were able to challenge each other with new ideas or thought provoking questions.

    Each week, everyone in our class was able to contribute new information or a new perspective on the “article/disease of the week”. It was challenging to look at diseases from a multidisciplinary lens. We also stressed the importance of sharing science with the general population. While innovative research, conferences, and scientific literature is important, it is also important to communicate that information to the general public in understandable terms. Often times in society, this aspect is overlooked. We learned ways to be concise and explain things in a way that was educational and accurate. Communication in different mediums was a skill we utilized a lot in this class, with presentations, written essays, partnered discussions (or speed dating as we liked to call it), and blog posts. The practice of sharing scientific findings with the general public was especially achieved through the blog posts. We also were able to practice our artistic skills and abstract thinking to reduce complicated ideas into simple drawings or ‘ARTstracts’. Some of us who aren’t as artistically gifted found this to be a difficult component to the blogs!

Because many of the diseases result in degeneration and death, it elicits the need for a cure to be found. Before treatments can be discovered it is important to understand the pathogenesis and pathways that are disrupted during this disease states. Many of them are very complicated and have lots of difficult components and potential causes. We started the class with a foundation on some of the basic pathways involved in cellular metabolism and maintenance and then applied this knowledge each week.

            Week after week we were able to tackle difficult diseases with complicated pathways. We would dissect them, question them, investigate them, and discuss them. Our Friday discussions were always interesting, and usually took tangents with deep thought questions and social implications as well as application to our own lives. Being able to discuss the science, and culture of diseases with a group of fellow college students is quite rewarding. Sometimes I think we forget that most people do not wish to discuss the adenylyl cyclase pathway for 70 minutes on a Wednesday. Yet we plugged along tackling one problem at a time – often leaving with more questions than answers. The more we learned, the less we feel we know! While this concept is frustrating, it also leads to inspiration and innovation that I hope we are able to bring to the world one day.

We also split into teams and worked on a community action project which was another way to bridge the gap between science and the general public. My group looked at eating disorders, especially on campus and with athletes. By holding a talk on campus for students, coaches, and teachers we were able to reach an audience that normally would not hear about the role of neurochemistry in eating disorders. It is important to raise awareness, and keep people educated and informed as to what is going on in our bodies.

            I felt like this class was a good way to cap off my time at Concordia. It was a good culmination of many of the courses I have taken here at Concordia. I know I personally was able to connect Vaccinology, Anatomy and Physiology, Psychology 111 & 206, Immunology, Microbiology, Religion and Science, Organic Chemistry, Biochemistry, and Embryology with this class. On top of that my classmates had other classes and experiences to add to it! That just shows how important it is to have that encompassing experience that can connect many fields and ideas. The ‘liberal arts’ way of thinking is very important in approaching some of the issues we are going to face in the future. Having a wide basis of knowledge allows you to think more critically and connect dots between two seemingly unrelated fields.

As described in detail above this class has hit all the liberal arts goals: to instill a love for learning, develop foundational skills, develop an interdisciplinary understanding, examine culture, ethical, physical and spiritual self-understanding, and encourage responsible participation in the world.

You have probably seen the muscle tremors that affect Parkinson’s patients.  Parkinson’s is a disease that kills dopamine-producing neurons in the brain.  While traits like intelligence, personality, and memory can decline, the most damage happens to the motor neurons that move our muscles.  Over a period of decades, muscle control gradually declines in Parkinson’s patients.  There are only a few treatments available for Parkinson’s, and they can only slow the progression of the disease or deal with the symptoms.

In the good old days as some people would call it, if you get hit in football or any sport and you were knocked out it was almost seen as a sign of weakness.  No man went to the doctor to see what was actually going on in the brain, instead it was recommended to just “shake it off”.   However, with the bombshell report that the National Football League was hiding research about concussions and the potential lifelong effects that could result from multiple concussions, the research has become abundant.

Before discussing the research it is important to see the scope of how many concussions actually occur in the United States every year.  According to the Centers for Disease Control and Prevention (CDC) in 2013 about 2.8 million Americans were diagnosed with a Traumatic Brain Injury (TBI), most of them being mild TBI’s or as they are commonly known as concussions.  These TBI’s accounted for 50,000 deaths in the United States alone.  Among all the concussion diagnosed every year it is estimated that 70,000 people experience permanent damage to their brains. One interesting fact, is that the most common sport that causes concussions is not football, it is actually cycling.  However, football still experiences just over 36,000 annually.

As a result of a concussion many problems can arise.  Cytoskeletal damage can arise because the force of a concussion can cause the complex microstructural components formed by neurons and glia to be damaged. This damage to the cytoskeletal complex can also cause axon dysfunction.  This means that the axons on neurons can be overstretched causing them to become overly porous to excitatory molecules.  To the extreme end of this the axons can actually be snapped off at the axon hillock.  This is severe because this prevents axons from sending action potentials and communicating with the rest of the brain.  This can cause cognitive deficits and a lack of communication in the brain.  One other main contributor the symptoms of a concussion is increased inflammation.  The upregulation of cytokines and cytokine genes causes an increase in stress on neurons.  This increased stress if it is prolonged can ultimately lead to cell death and an overall loss of neurons.  Either way a concussion can be catastrophic, however what has arisen over the past several decades is the ability to see the effects of a concussion.

This is where the imaging arises. The first form of brain imaging is Diffusion tensor MRI (DT-MRI). It works by sensitizing the MRI signal to the random molecular motion of water molecules (diffusion) by addition of ‘diffusion encoding gradients’ to a standard MR pulse sequences.  Water molecules are more likely to travel down white matter (neuronal pathways) than they are to leave these pathways.  This allows you to visualize if any of these tracts are damaged, hence seeing if there is a concussion

The second method for visualizing TBI’s is functional magnetic resonance imaging or functional MRI (fMRI).  This works by using MRI technology that measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases.  So in essence decreased blood flow to a region of the brain would imply that there is damage to this area of the brain.

Based on the images above it is clear that concussions are not good for the brain and should be take very seriously.  If you or someone you know has a concussion make sure to see a doctor to plot a course of action and an effective treatment.

The Capstone Course Serves as a Sturdy Foundation for the Future
No project is complete without the finishing touch. A Christmas tree lacks luster without the star on top. A painting doesn’t shine without the varnish finish. A Concordia education is incomplete without a capstone course. As a chemistry major, the logical choice for my capstone class was neurochemistry, and I feel it was the perfect finishing touch to my Concordia career.
When I began my freshman year, I was set to be a chemistry major. I was good at chemistry and learning in lecture came easy. Neurochemistry was the first class I took that focused on independent learning, and it happened to be in my last semester at Concordia. I was initially nervous about the amount of biology at the beginning of the course but once we delved into the article analysis, it didn’t seem to matter as much.
While I was doing research at the University of Minnesota this past summer, the grad group I was part of had weekly “Lit Club” where they read current literature published that was similar to their research. I would sit through the meetings every Friday morning thinking that I would never be able to understand the articles they were reading. In neurochemistry, the articles were about the brain and signaling pathways of which I had no background knowledge. I learned that even though I lacked background knowledge, I was still able to understand the general message of each article on my own. It gave me hope that when I am part of a grad group in grad school, I will be able to understand the articles on my own and be able to contribute to the group discussion.
However, this is not the only reason this course has prepared me for the future. It has also taught me to enjoy reading articles of current research findings. Reading articles for class has seemed like a chore in the past, but for neurochemistry, I looked forward to reading about diseases and how altered brain functions resulted in signs and symptoms. I can apply this new enjoyment to my future by continually learning about new scientific discoveries.
As my time at Concordia comes to a close, I have looked back at everything I have learned along the way. Not only have I learned necessary chemistry knowledge, but I have now also learned how to apply my knowledge and continue learning on my own.
I truly believe that this capstone course was the perfect finishing touch on my Concordia education. Learning how to continue learning on your own, for scientists at least, I think is crucial to being a successful scientist. I look forward to my future and learning even more about subjects that I love.

Stress and Anxiety. Two words you hear often now a days. Especially if you are like me a college student. These two factors can negatively impact our lives and make life much more difficult. These two things are caused by our non-stop desire to be productive. People vary between how they deal with stress and anxiety differently and people differ in how easy they get stressed out or anxious. It’s weird how that is a widely accepted truth. But how does this occur? There are a couple of different reasons why.
A review article in the frontiers of psychiatry reveals that it is the formation of memories attributed to stress and anxiety. Although our bodies are designed in a way that you can make strong memories of stressful events so that in the future you can avoid them. When I say stressful event, the most likely stressor that a human would activate this mechanism would be a wild animal attacking them in the woods or something along the lines of that. But with the modern civilization and the way society is today we do not experience these sort of stressors often at all. This biological mechanism in the brain gets hijacked by the “stressors” we experience as humans almost everyday in the modern world. The paper describes that the adrenal gland releases corticotrophins, which are responsible for releasing adrenaline in the body and increase heart rate and alertness, which is characterized with stress and anxiety. In people with stress and anxiety disorders this becomes dysregulated and this very mechanisms attributes to the formation of the memories associated with the stressors.

In combination with increased corticotrophin release glutamate signaling pays into factor within stress related memories as well. Cellular mechanisms such as a dual histone activation of a protein complex called H3S10P-K14ac increases the production of proteins called c-Fos and Egr-1. These proteins are directly involved with forming strong memories and consolidation processes as well. This underlying mechanism can thus cause an increase of “noisy” thoughts that are characterized with the intense memories of the stressors, which can cause attention deficits. The Prefrontal cortex gets dysregulated as a result of this cascade because the connections between the hippocampus and the amygdala become desensitized.
There is a wide array of medications for anxiety, they include, Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norephenipherine Reuptake Inhibitors (SNRIs), and Benzodiazepines. The mechanisms for SSRIs and SNRIs block the reuptake channels on neurons of these specific neurotransmitters that play important roles in mood stabilization. Recently it has been described that Histone modification of the phosphorylation and acetylation of the histone H3 complex (H3S10p-K14ac), leads the activation of gene transcription of IEG genes, which facilitate strong memory formation. This mechanism is strongly linked to anxiety disorders and it appears Lorezapam and well-known benzodiazepine blocks the phosphorylation and acetylation of the histone complex. Other anxiety medications and their mechanisms relating to these histone modifications are not well known. However, It has been found that the mechanism for benzodiazepines like lorezapram acts on GABAergic neurons. This relationship could possibly lead to the inhibition of the phosphorylation and acetylation of the histone complex. They are allosteric modulators of the GABA-A receptors. These receptors ligand-gated chloride channel and when activated hyperpolarize the target cell allowing Calcium ions to flow in. Benzodiazepines bind to these receptors in a specific pocket that induces a conformational change and allows GABA to bind.
It’s a terrible cycle. Stress and anxiety when in high doses can be maladaptive for everyone as indicated by this article. However, in this day and age these things are unavoidable. This is why developing a deeper understanding of these aspects and what they can do to a person is important. It is also important to manage these things so that the stress and anxiety levels to become too high where you can develop problems that can be very hard to deal with.