I was intrigued by one of the articles I stumbled across in the news a couple weeks ago. Neuroscience research has shown that Oreos are more addicting than cocaine. According to the neuroscientists conducting the study, eating Oreos stimulated more neurons and created greater release of dopamine than illegal substances, such as cocaine. This is just one of the example of widespread function of dopamine. I feel like most of the behaviors and discoveries that we hear about in the news are explained by dopamine signaling pathways. For example, dopamine is involved in movement, emotions, reward, pleasure, and addiction.
However, in class this week we discussed another role that dopamine plays in the brain through a unique signaling pathway. Dopamine binds to the D2 dopamine receptors (a G-protein coupled receptor) and causes its effects by increasing levels of cAMP in neurons. However, scientists are starting to learn that dopamine may also influence the Akt/GSK3 pathway as well. As this point, some people reading this blog post are thinking, “What is the world are you talking about?” and “Why the heck do I care about these things?” The basic idea here is that dopamine is acting through an additional mechanism that may provide useful targets for antipsychotics, psychostimulants, and antidepressants that are used to treat schizophrenia, bipolar, and Parkinson’s disease.
First, let’s look that the Akt/GSK3 signaling pathways under normal conditions. When dopamine binds to D2R receptors, this causes a signaling complex of proteins to form. This complex includes a magnesium ion, beta-arrestin 2, PP2A and Akt. The PP2A proteins regulates the activity of Akt when they are bound together and inactivates Akt. Like a line of dominos, PP2A controls Akt and Akt controls the activity of GSK3. When Akt is inactive, GSK3 becomes activated. Overactivation of GSK3 is thought to play a role in the pathogenesis of some neurological and neurodegenerative diseases.
So, how do pharmaceuticals target this pathway to treat conditions such as biopolar, schizophrenia or Parkinson’s disease? Lithium is one therapeutic agent that is commonly used to treat bipolar. Until recently, little was known about the mechanism of action. Research has shown that lithium affects the Akt/GSK3 pathway in two ways. First, lithium ions are similar to magnesium so they compete for a spot in the signaling complex of the Akt/GSK3 pathway. Without magnesium to stabilize the complex, Akt remains active and GSK3 remains inactive. Lithium has also been shown to directly inhibit GSK3. Antipsychotics used in schizophrenia also target this signaling pathway. For example, haloperidol increases activation Akt and inactivation GSK3. Atypical antipsychotics activate Akt or mimic its effects by directly inactivating GSK3.
Research from “Beyond cAMP: the regulation of Akt and GSK3 by dopamine receptors” suggests a new pathway that is regulated by dopamine and is implicated in the development in many neurological diseases. Further research is still needed to answer questions about other players in the pathway. For example, what proteins or molecules does GSK3 target when it is active? Beta-catenin and neuregulins have also been shown to play important roles in the signal transduction pathways. I would still like to know more about the regulation and control of these mechanisms, as well as what other roles this pathway plays in the brain. The Akt/GSK3 pathway may prove to be an effective therapeutic target for treating neurological disorders related to dopamine.
It takes many brains to understand our own… Capstone Experience
When looking back on my experiences throughout the semester, particularly in my capstone course Neurochemistry, I think about the ability to get your point across fast. It sounds simple right? Well now imagine the topic is one of the scientific fields, and you have to sift through copious amounts of information and then crank out roughly a three minute summary of what actually should matter to a group of future scientists. It was a great experience for someone like me who loves to talk many an ear right off.
I would probably say one of my favorite discussions we had during the year was the discussion on concussions. It is a super interesting topic for someone like me, who was able to bring my love of sports, a tiny amount of biochemistry knowledge, and a “dust yourself off” mentality. Well, I had not had much experience with the science behind concussions and when I would see an NFL player get hit in the helmet prior to our classroom experience I would just enjoy the play as usual. It soon became clear that the off the field arguments about concussion treatments between the NFL players association and the NFL itself actually had a lot of people hanging in the balance. I learned that people sustaining multiple concussions actually had many long term issues associated with them.
The concussion debate actually represented everything that I would expect from a capstone course. When I thought of a capstone, I thought of the culmination of all my years here at Concordia and how I could use them to tackle a social problem using my acquired knowledge. The issue of concussions I soon learned however can’t be decided with only chemistry knowledge. Throughout the semester I came to appreciate psychology more and more. Before the class I sometimes wrote them off as the many students one floor down coasting to a 4.0 GPA, while we in the chemistry department struggle to survive. There was a large demographic of chemists in our classroom this year, but we had a couple psychology and neurosciences students that really held their own in the realm of academic discussion. I really gained an appreciation for their knowledge of the human brain as well as what chemistry was going on.
With help from our instructor, and the group of diverse students I got to know in our classroom this year I know that my grasp on things outside of my small college has been increased. I know that if I am ever to try and tackle a problem out in the real world, it will take more than just my knowledge alone, but a great supporting cast as well!
Alcohol, a Three-Headed Monster
Alcoholism is an issue in the United States that most people try to understand. In the class Neurochemistry, the chemical world often bumps heads with the psychological world. Alcohol abuse and ethanol’s effects on the brain were a great place to have that discussion again. It should be added that there are large influences from society as well.
Being twenty-one years old has its advantages in a college area like Fargo-Moorhead, you can legally drink out at the bars and take advantage of the specials that the area has on alcohol that are almost unmatched anywhere else. Think to yourself; is there a night of the week that there isn’t a drink special somewhere in FM? It is so available and widely accepted especially at the college age that its consumption around the area is common. However, leaving society’s role in alcohol consumption, the psychological role in alcohol consumption, addiction is the primary reason for the problem known as Alcoholism.
Alcoholism or being addicted to alcohol on a psychological level is a problem that can be seen in many different age groups, genders, and ethnicities. What is the difference between being chemically addicted and psychologically addicted?
Well it was learned that in people who have alcoholism, there is a strong amount of activity in the pleasure center of the brain. This was seen using PET scans of alcoholics verses the scans of their non-alcoholic counterparts. More changes in the brain cause by alcohol addiction are that it can alter mood even when sober. People who were addicted to alcohol actually showed greater responses to negative stimuli than people lacking alcohol addicting. This might help explain why most alcoholics turn to a strong drink on a bad day. It helps their brain try and equalize their reaction to negative stimuli. It was shown that through the addition of alcohol many of the alcoholics had a lessened the response due to negative stimuli.
People usually develop a chemical addiction to alcohol along with their psychological addiction; this is part of the reason that it is so hard to rid someone of their alcohol problems. It effects their body giving them sickening withdrawal symptoms as well makes them lose part of their psychological mechanism for dealing with stress or other negative stimuli.
So whether the reason is social, chemical, psychological, or some combination of all three, alcoholism is a very tricky addiction to treat even with today’s medicine. It some cases it requires a lot of help from doctors, and family alike.
Getting Knocked Around by Concussions
“Just let them play the game!” I often find myself yelling this at the television every Saturday and Sunday. My weekends often are ritualistic in that I enjoy a nice rough game of football; whether it is collegiate or professional. In recent years however I have noticed quite a bit more laundry (penalties) on the field, because the NCAA and the NFL are really trying to limit injuries such as the ones we discussed in class. The biggest injury in football that applies to neurochemistry would have to be concussions.
Do not be fooled by the habit in the NFL of a player who has “concussion-like” symptoms only being out of playing for about a week. It was discussed that the problems cause by concussions are very real, the glucose metabolism of an individual affected with a concussion drops below normal levels from minutes after the collision and can last up to weeks after the collision. This causes immediate damage to the parts of the brain such as focus and motor skills. It is even more dangerous for a person who has already had a concussion to continue playing, because they risk having another concussion. It has become an issue among NFL retirees who dealt with multiple concussions during their careers and now have many health problems because of it.
The scarier problem is that the effects of concussions are greater on younger players. The brain continues to develop up until the mid to late twenties. This means collegiate athletes who try to mimic their NFL counterparts by only staying out for a week or two are actually putting serious risk to their future mental health. Their developing brains, whether they admit it or not, are more seriously affected by trauma than an older player.
Another interesting question is: “Why is there not a universal testing system?” Well in class it was learned that there actually is a very successful test out there that has been adopted by several major sports organizations; it is called the ImPACT test. It is a computer based system that deals with “cognitive efficiency.” The patient submits a baseline at the beginning of the season and that is a stored scored for memory, reaction time, and visual reaction. The ImPACT test, while used by the NFL, MLB, and NHL, has only been mandated by the NHL.
So concluding what to take from the neurochemistry on concussions: it affects most people differently depending on the stage of brain development, it is a large problem for most contact sports, there is a system out there to help diagnose, but just because it is available does not mean it is implemented.
I am not trying to scare people away from letting their children play sports like football, but I hope that we just pay extra attention to what is happening with their mental health as well as their physical health when we put them out on the field. They represent the minds of the future and we don’t want them being knocked around too much.
Losing Control of the MAPK during Finals Week!
In the spirit of finals week, I think about a discussion on the MAPK pathway in my neurochemistry course, and the first thing that comes to mind is not a particular enzyme or disorder, but instead I think about my greatest fear. Could it be a final exam? Could it be not getting that particular job after graduation? No, my greatest fear, which is commonly shared by many people, is losing my sense of control. It is this idea of “losing control” which then builds into the things that can go wrong along the MAPK pathway. Imagine not being able to remember any of your loved ones, or not being able to control your body because you have involuntary movements. Diseases responsible for these types of feelings, Alzheimer’s, Parkinson’s, ALS (Lou Gerhig’s Disease, all can result from abnormalities and disregulation of the MAPK pathway.
What can cause disregulation of this pathway? Oxidative stress; it is something that seems to come up on a weekly basis in our classroom discussions. Free radicals present inside the bodies that are left unchecked by defense/clean up mechanisms can cause a lot of damage to a variety of different cellular processes. It is a very difficult task to limit the amount of oxidative stress on the human body, and specifically in the MAPK pathway.
The MAPK pathway is comprised of countless intricate proteins, receptors, and other subunits that can apply to any number of processes within the cell. In order for researchers to try and tinker or change certain parts of the pathway to protect us from diseases caused by oxidative stress, they run the risk of negatively affecting other mechanisms which are dependent on the products of the MAPK pathway.
So even after science has uncovered linkages between the MAPK pathway and these serious illnesses there is little that can be altered now as far as cellular mechanisms. The complexity of the human brain strikes again! However, I should not fool myself or anyone else into thinking that a defect in the MAPK pathway of the brain is the only way to get Alzheimer’s, because as we learned earlier in the semester there also may be a link between Alzheimer’s and insulin resistance. So for now all one can do are the little things; just like during finals week. Little things like eating healthier once in a while and adding some anti-oxidants into my diet may prove to go a long way. So would studying for that final exam.
Concordia's Capstone Experience
I took Neurochemistry this semester in order to fulfill my capstone course requirement for my major. What it means to take a capstone course at Concordia is that we take a special class which is suppose to examine an important subject in the world using the skills which we have acquired over our years at Concordia and to find out whether the qualities that Concordia’s mission statement espouses have been instilled within us. These qualities are a love of learning; foundational skills and transferable intellectual capacities; an understanding of disciplinary, interdisciplinary, and intercultural perspectives and their connections; an examined cultural, ethical, physical, and spiritual self-understanding; and responsible participation in the world. Thinking back on my experience in this class it I can say that I was able to use these qualities within myself for this class.
During the first quarter of this school year we learned about basic neurotransmitters and receptors, which laid the groundwork for our understanding of the articles that were to follow in the second quarter. In each article we read we were asked to identify subjects that we didn’t understand and present to the class on what we discovered in our research of each of the topics. We then had a discussion on the last day of each week, led by a pair of students, where we discussed the implications of the research and what it meant for society. This time was also a time to share personal knowledge of the issues that were being brought up. Testimonials about friends and family who suffer from the disorders being discussed in the paper. We also talked about what we were taught in our other classes about the disorder.
Looking back I think that as a class we had absorbed the true lessons that we had been taught over our time at Concordia. We had been taught more about how to approach a problem rather than what the answer to these problems were, which I think is a wise choice. The issues that we discussed in class were problems that would require more than a few bills passed in Congress, or a few new prescription medications on the market to solve. The problems that we discussed more often than not ended up being chalked up as a problem that was too difficult to solve in the hour and ten minutes that we had for discussion and we learned from our time in this class that this was okay as a lot of the papers that we read said that a lot more research would be needed to understand the numerous issues the problem that the authors were focusing on. I think that one thing for sure we could say as a class is that our time in Neurochemistry taught us that one scientific article isn’t going to put all of our questions to rest. Rather the search for answers is a long and exhausting, but at the same time exhilarating process. I think that if more people took a course like ours they would stop being so argumentative and really start discussing the issues that we face because the way forward is hard enough without us pulling each other into a fight over trifling details.
A Reflection of My Neurochemistry Experience
The experience I had in my neurochemistry capstone incorporated more of the goals for liberal learning than any other class I have taken at Concordia. Although I am biased, as I have always had a passion for neuroscience and believe that is has so many answers to questions that are raised in today’s society, I do not doubt that my classmates would similarly agree.
Each week of class we were given a scientific literature review to read and ask questions about. The beginning of the week started with a general discussion about the paper and questions that we had about the paper. As a class, we accumulated a list of topics we did not quite understand in the paper and/or wanted to know more about. At the end of class, we divided this list amongst us so that we would each be responsible for investigating a specific topic for the following class. Then, at the next class, each of us would teach our classmates about the topic we had researched more about. This information helped us to grasp the concepts of the paper far better than we had on the first day. Finally, at the end of the week, the class divided into two large groups to discuss the paper. There were not any rules to the conversation; in fact, we often strayed from the topic of the paper (eventually finding our way back).
The topics that we covered throughout the semester ranged from concussions, to autism, Alzheimer’s disease, to marijuana use, obesity, to alcoholism. The neuroscientific literature that exists in correspondence to these topics is incredible, and immensely important to progressing forward in learning about these issues. Until we learn how the body’s most important organ (again, biased), the brain, is involved in these diseases or addictions, we cannot make advancements towards treatments, or therapies, or prevention strategies that address these national and worldly issues.
The class encouraged me to pull information from so many areas of my liberal arts education as well as my own experiences. I was inspired to use my prior education as well as my new knowledge of the topics to contribute to our fascinating discussions. Actually, this was my last class on Fridays, and I always left class with our discussion still buzzing in my head hours (or sometimes even days) later. I felt that our in-class discussions stimulated within me a sense of responsibility I had to society to address these issues, even if that was simply through spreading the word about the information I had obtained.
In my opinion, neuroscience has so many answers and can contribute to putting society on a path where we are consistently “bettering” ourselves. I view neuroscience as a way to discover treatments for neurological disease and raise community awareness about neurological disorders so that we are more accepting of others, ultimately leading to a more cohesive and tolerant country.
Autism and Xenobiotics
“Methylation and redox buffering activities are equally supported by the methionine cycle and transsulfuration during normal redox conditions. [However], during oxidative stress multiple adaptive mechanisms shift the flux of sulfur resources toward GSH synthesis, including reduced activity of methionine synthase, increased activity of cystathionine-b-synthase (CBS) and decreased activity of cysteine dioxygenase (CDO). Lower methionine synthase activity reduces methylation, including dopamine-stimulated phospholipid methylation and its role in attention.”
For some readers, this paragraph might be slightly overwhelming. However, the phrases that are most important to pay attention to for the rest of this blog are italicized; normal redox conditions, oxidative stress, reduces methylation, role in attention. What do these phrases have in common? They are all important pieces in the story of autism.
Autism is a developmental disorder that affects the brain’s normal development of social and communication skills. The exact number of children with autism is unknown, but the number of diagnoses seems to be increasing. However, it is also unknown whether this is because the disorder is becoming more prevalent in the population or because there is an increased ability to diagnose the disorder.
There is little known about what causes autism, but scientists speculate that xenobiotics, or chemicals found in the body that are not normally produced by it, play a role in the development of the disorder. Researchers speculate that environmental insults (chemicals) promote oxidative stress and reduce methylation that leads to developmental delays and attention deficits as well as a lack of synchronization of neurons that is characteristic in autism.
This raises a concern for the chemicals that we encounter throughout our daily life, especially when these chemicals have such adverse effects on our bodies. It makes you wonder what other diseases these chemicals can induce in our bodies. Out of my own curiosity, I did the inevitable, and Googled it. What I found was slightly disheartening. The Agency for Toxic Substances and Disease Registry divides the bodies systems into categories and lists possible contaminants that might affect that particular system and where these contaminants might be found. For example, lead had negative effects on the renal system and can be found in old paint and outdate plumbing and nickel may adversely affect the skin and can be found in cement. The list was already quite extensive and it did not even include all the chemicals that we can be exposed to in our lifetime.
I sometimes wonder if society is so concerned with making life “easier” and more “efficient” that we forget that those things that might make life easier or more efficient for us also contain contaminants, contaminants that can harm our families and us. Or, for example, induce a disorder in children that negatively affects their social development and attention abilities.
If further research accumulates evidence pointing to certain chemicals that induce autism in children, will efforts be taken to take these chemicals off of the market? Due to the economics, I sometimes wonder if the necessary steps would be taken to do so, but ethically, it must be done.
Reflecting on A Cobber's Capstone Experience
When I first registered to take Neurochemistry I was nervous to say the least. At the same time as taking Neurochemistry I was also enrolled for Biochemistry. I felt at a real disadvantage since I had no prior Biochemistry background and my experience with biology and anatomy was on par with a 7th grade health class (or at least it felt like it to me). My adviser and professor of the class assured me that the class would turn out fine for me. Skeptical, I entered the class with expectations that the course would entail heavy lectures and horrendous assignments. I was meet with a completely different experience. The class turned out to be a lot more low-key and individualized than a regular class.
Lecture was not the main focus of the course. The idea behind the class was all about becoming an independent learner, someone who is capable of reading a scientific research article and critically analyzing the aspects of the research. The class was very much discussion based and I must say it was one of the best discussion based courses I have participated in. It was hard not to find something to talk about. Our topics, such as: obesity, alzheimer’s disease, alcohol, autism, opioid addiction, and concussions, allowed us to extend our discussions to the realms of sociology, psychology, chemistry, and personal experience.
Because I was taking Biochemistry at the same time of this course, the two complimented each other well. Often in Neurochemistry we would discuss a topic looking at specific pathways, enzymes, neurotransmitters, and proteins which I would later hear about in Biochemistry (mainly because Biochemistry progressed kind of slowly). I was able to take what I learned in Neurochemistry and use that to help me understand the basics, which I received in Biochemistry. It sounds a little odd that studying such in-depth topics would actually help me understand the fundamentals of Biochemistry, but because I was able to connect the basics with an application I could see the importance of what I was learning. This application of Neurochemistry to other areas of science and life was one of the major reasons I enjoyed the class.
Compared to the all the classes I have taken up to this point, Neurochemistry wasn’t the hardest class but it did demand and push me the most. Blogging was in part one of the reasons that Neurochemistry pushed me. I have to say I wasn’t the most comfortable with having blogging as an assignment. The one thing blogging did do for me which I appreciated was cause me to reflect on the topics discussed in Neurochemistry. If you didn’t know Concordia College is all about reflecting on one’s personal experiences and this capstone class definitely encompassed this mentality. This class allowed me to apply chemistry outside of chemistry. I was able to broaden my view outside of a simple restricted tunnel. Neurochemistry in a way revitalized my love of chemistry, because I was able to make connections with chemistry to areas I would have never thought could be related. Overall, I enjoyed my capstone experience and will take with me that science, specifically chemistry, has far more application in society that may be apparent at first glance.
It's More Than Just a "Choice"
Approaching a stoplight, you see a homeless man standing on the corner where you are about to make a left turn. He is holding a piece of cardboard that says, “Homeless. No food. No money. Anything helps.” You cannot help it, your mind instantly goes to the assumption that the five dollars you could give him sitting in your wallet will go straight to the liquor store because the man MUST be an alcoholic. Although it’s understandable why some people might assume this, the effects of such assumptions are completely unfair. The stigmas that arise from these assumptions are unfair to the person and do nothing to help them get back on their feet.
I have often wondered why diseases that involve, for example, the heart or the lungs seem to be “socially acceptable”. Is this because, historically, there has been a more biological, medical explanation for such diseases? Sometimes, I feel that this is the case. It seems that when society has a scientific explanation for a disease or disorder, we are more willing to accept and understand what the person is going through. For example, society is more willing to accept someone who has coronary artery disease or emphysema because we recognize that these diseases are out of the person’s control, that it is not their CHOICE to have intense chest pains or a chronic cough. More recently in our history, disorders of the brain are also becoming more accepted and understood by the public, such as bipolar disorder or schizophrenia. Instead of believing that the person is simply “moody”, or “crazy”, we understand that their brains do not function as the “normal” person’s does. This means that society is more willing to understand their condition and exerts effort to help the person maintain a normal lifestyle through therapies and/or medications.
Unfortunately, this is not yet the case for addictive disorders such as alcoholism. Society places a great stigma on those who are addicted to drugs and/or alcohol, which does nothing to help the person or the country as a whole. We are quick to associate alcoholism with bad choices and irresponsibility. “Why can’t they control their drinking? I can..” are questions that may often be raised when encountering someone who has a history of alcoholism. What society does not understand is that, just as coronary artery disease and bipolar are diseases that can be “explained” scientifically (although much is still unknown about the diseases), so too are addictive disorders. Genetics and environment have an affect on the body and on a person’s susceptibility to become addicted to drugs and/or alcohol. Too often we assume that it is simply a matter of choice for a person to quit abusing drugs or alcohol, but we forget that far more is occurring within that person than we could ever understand without experiencing the addiction ourselves.
Not only does science explain why addicts experience an almost unbearable withdrawal from substances when they try to quit or refrain from using, but science can also point to childhood experiences and environments that increase a person’s likelihood of experiencing addictive substances and their susceptibility to addiction. When we understand that addiction is more than just a “bad choice”, we are more willing to understand and be empathetic towards a person’s state of wellbeing rather than climbing aboard our high horse and passing judgments on them.
This week in class we reviewed a scholarly literature review that looked into the chemical and biological mechanisms that played a role in a person’s susceptibility to alcoholism as well as the dysfunctional mechanisms that exist in the disorder. Alcoholism is so much more than simply a “bad choice”. Yes, it IS a person’s choice to take a sip of alcohol, but it is naïve to believe that this is the only piece of the story. Just as we accept those with other diseases, we must also accept those who have addictions, as neither the person or the country move forward until we do.