Before taking my capstone course at Concordia, I definitely had a bias towards any course that carried the “capstone” tag. The sound of the word itself had always led me to believe that any course with this title was one that was designed to be extremely rigorous and in a way the “final mountain” to climb in order to graduate. But as I conclude my semester long neurochemistry capstone course, I have realized that it is the exact opposite of what I led myself to believe. Not in the sense that the class was easy by any means but more so in the sense that this was a class that was set up in a way that was completely foreign to me.
Instead of learning in the classical classroom setting where the professor lectures and the students take notes only to be followed by quizzes and tests in the future, we were really challenged as students to learn in a new way. All of a sudden tests and assignments didn’t matter as much in this class. We still had them, but not in the general sense that we become so accustomed to in our first 3 years of college. We found ourselves being graded on critically thinking and real-world problem solving. We sought ways to create targets for new drugs and diagnose diseases in a different manner, things that seemed like they had real world application in the world right now. We learned how to take a problem, think critically, and then communicate results and engage in dialogue about the issue. I think back to our Wednesday’s where each of us had a specific topic that all pertained to one large problem or topic that we were discussing about as a class. Explaining our topics to fellow classmates caused us to engage in discussion about our topics, the problem as a whole, and how to solve the problem.
One of the things that I am most happy that we did was the Friday discussion time as well as the blogging. This forced us to take concepts that we learned in class that were extremely scientific and deep and take them and communicate them to a general audience while still explaining the science and getting a point across. The discussions led us to apply a topic to not just the scientific or medical community, but a wide range of other communities as well. This class in short was the first class that I think I have ever taken that is a science class but at the same time explains science in terms of society and politics and everything else at the same time. This is why it was such a different way to learn, because it put science in a completely different light than we were used to.
So as I have said before, I am extremely pleased with my capstone experience. It was nothing like I had thought it was going to be and everything that I thought it should be. It had me take all of the knowledge and skills that I have gained while at Concordia and put them into the area of study that I am most interested in while at the same time challenging me to apply these skills to the real world. It is safe to say that my view of what a capstone course is has completely changed. More than doing some big project or paper, this class has showed me what it is like to apply what I know to society in order to make a difference. After all, shouldn’t that be what a capstone course is all about? I think this type of class is what seniors need as we all prepare to graduate and go out into this world on our own.
The odd truths about autism and its diagnosis
It’s hard to find a disorder in this world that is more tricky than autism. Unlike the having to flu for example, it has become much more trivial as to determining if someone has autism or not. Many people are aware of what autism is, but unaware of how it is diagnosed and how we can maybe treat it.
There are many odd sociological trends as to the diagnosis of autism that don’t really make sense in the realm of how diseases are generally diagnosed these days. Long story short, much of what is used in the diagnosis of autism is based on largely subjective criteria in my opinion instead of the hard scientific facts that we have become accustomed to. For example children with parents who are upper-middle class and higher are more generally diagnosed with autism. Now how can this be? Well it’s no secret that these families are able to afford top quality medical care as well as multiple opinions. Social status aside, I think that the real problem lies within the criteria that have been set out in diagnosing this disorder.
These criteria are fairly numerous as you can see below.
This figure just gives an example of some of the criteria that are used in determining if someone has autism. Granted this from the DSM-IV and not the DSM-V, it still gives you an idea of the things that medical professionals look for. Like I said before, these criteria are so subjective. Once doctor could pronounce a child to not have autism, but the next one could pronounce the same child to have autism. That is my problem with this system. Also, medical professionals are trying to diagnose children at a younger and younger age all the time. I think that it is unfair to judge a 2 year old child on “failure to develop peer relationships” among other criteria. I mean what are you supposed to do, watch the kid at daycare and see if he plays with building blocks effectively with the other kids? And how do you assess children who just have a naturally quiet personality? I can’t help but think that some perfectly healthy yet quiet kids would be unfairly diagnosed as well. I think that this is at least in part the reason why we are seeing such an increase in autism diagnosis in the past decade.
Now that I have vented a few of my opinions about the system I can explain some of the science that is behind autism. Limited science has shown that autism is linked to CNV’s in a person’s genome. These are copy number variants, which are basically just alterations to a few different genes in the genome. These alterations of genes make cell adhesion very difficult and in turn make it difficult to form synapses and achieve synaptic plasticity. Unfortunately there aren’t really any drugs that can change a persons’ genome back to a healthy one. With that being said treatment options with autism revolve largely around therapy, as no real medications have been tested with great efficacy. I think that this paper has made me more aware of autism above anything else. It has helped me to form the opinion that we definitely need to conduct more research to learn more about this disorder, as it seems that we don’t have too much to go on at this point when compared to other disorders.
Is fat our fault??
America is fat. Fat is America. You can say it whichever way you choose but the message is still the same, we are the most obese country in the world. But is it our fault? We recently read a paper that explored the possibility of obesity being a brain disorder rather that a disorder that is caused by our diets and overeating. Shockingly there is a significant amount of evidence that would lead us to believe that obesity is indeed a brain disorder. However, before you go out and buy yourself a Big Mac because “it’s not my fault that I’m fat” you should listen a little closer.
This article made the case that obesity as a disease starts for somebody while they are in the womb of their mother. They argued that the chances of a child having the brain disease of obesity is predicated on the diet of the mother. When a mother eats a very unhealthy diet, then those nutrients are shared with the child in her womb. The child becomes accustomed to the high level of fat in his or her diet and when they are born, their brain is already programmed into the diet that their mother had. The researchers also conducted a study in mice that supported their argument that offspring exhibit the dietary trends of their mother. This is some supporting evidence that obesity could in fact be a brain disease.
To further the argument, the paper as well as our class took a look at two different types of neurons that are in the brain that have both been linked to obesity and/or appetite in general. The first was NPY/AGRP neurons, which are neurons that seem to stimulate appetite when people are hungry. This obviously is something that is overactive in obese people. Personally I looked at the other category of neurons, the POMC neurons. These neurons decrease appetite and tell your brain when you are full. These neurons are activated by leptin and insulin. Insulin of course is released after you eat, ordering your tissue to absorb glucose from the blood to make energy for your body. Leptin is the hormone that is released when you are full. Obese people have deficient POMC neurons. So when they eat, the body releases insulin and leptin but the POMC neurons do not become activated and so the brain is still under the impression that you are hungry, when really you may not be.
Sure all of these examples were nice to learn about, it was an aspect of obesity that I had never heard about. But take this with a grain of salt, because there is clearly other research out there that suggests that obesity is also caused by diet alone. I believe obesity to be a combination of both a disease, but at the same time a disease that was initially caused by the choices one makes about their lifestyle. So while research such as this gives us insight into potential treatments and drug targets to combat obesity, it should not reinforce the idea that overeating or unhealthy eating is acceptable. Like I said this problem is still largely in our hands. We need to eat right to get right, your body will thank you.
The search for a wonder drug…
Have you ever wondered if there is a wonder drug? A drug that does really anything and everything? Something that you can take and it will ensure your health for as long as you shall live? I think of the movie limitless, where this is indeed the case. Then I sink back to reality and realize that the only time you hear about a wonder drug is well, always. Every time you flip on the TV and a new drug ad plays on your screen for whatever the case (hypertension, depression, etc.) you can’t help but think how awesome all of these new drugs are, or so they seem. Unfortunately, our population shows that more often than not these drugs are not everything that they are all cracked up to be.
This leads me to an article that our class read this week that talked much about lithium and its use in the treatment of bipolar disorder. Lithium has been shown to do many marvelous things inside the cells of our brain. It protects neurons as well as helps in the consistent supply of nutrients that the cell needs to survive. Lithium activates the actions of what scientists call BDNF or brain-derived neurotrophic factor, which is a good thing. At the same time, lithium inhibits GSK3 and phosphoinositol phosphatases, which are both in pathways that lead to cell apoptosis. The inhibition of these pathways that would potentially lead to cell apoptosis is then a good thing. This is why lithium can be used to treat one of the widest spectrums of disorders that I have ever seen. Things like Parkinson’s, ALS, bipolar, Huntington’s, and even fragile X syndrome.
Based on the information that I have just laid out for you it really does seem as if lithium is the wonder drug that everyone, myself included, has been looking for! It can’t be that easy though right? Unfortunately, that is right. So don’t go chopping up batteries and putting them in your salad just yet (a joke, please do not attempt). While in class we had talked for almost 2 full days on how wonderful lithium is, leading everyone to believe that we should all be on daily lithium supplements. Since we were all so skeptical that just taking lithium could be beneficial we decided to research this topic more. What we found was that lithium is good yes, but excess lithium becomes detrimental to our health. The search for the wonder drug fails again.
What I can’t help but take away from this article is something that is way bigger picture that this article itself. Like I said in my opening, drug ads make every new drug seem like a wonder drug, as we did in my class with lithium. What I want people to realize is that the chances of a new drug actually being a wonder drug is not likely. I mean, it hasn’t been done yet so what evidence do we have that a new drug would be? I want to advise people to do their research when it comes to supplements and drugs because, like my class found with lithium, extra research often leads to the truth, which is something that can make us all healthier.
Should we be pumping iron?
Fe. A simple two letters on the periodic table signifying the element iron. The periodic table is for chemistry freaks though, right? Well that very well may be, as the only interactions that some people think they have with iron are in an industrial sense or going to the gym to “pump some iron.” Little do most people know, however, that this tiny element with the title of Fe, is one that not only is essential in your blood cells to carry oxygen but also one that is involved in Parkinson’s disease. In the words of someone famous, “You better recognize.”
Now, before reading this paper I was aware that iron played an important role in the body, but I’ll admit I did not think that it could possibly play a role in one of the more well-known neurodegenerative diseases. The title of the paper is a messy one so I wouldn’t beat yourself up too much if you don’t understand what it means after just reading it because I barely do. The paper is titled Targeting Dysregulation of the Brain Iron Homeostasis in Parkinson’s Disease by Iron Chelators. I dare you to say that five times fast, go ahead it’s definitely a mouthful. But the link between PD and iron is there. People who have PD have been shown to have a much higher level of iron in their system than people who do not.
So the question becomes, how do we regulate iron inside of our cells and our body? Iron in the brain should be kept at homeostatic levels. This is achieved by the IRP family of cellular receptors, which have been given the extremely clever and unique names IRP1 and IRP2. These receptors are very interesting in that when cellular iron levels become too low, IRP binds to ferritin, which prevents the cell from “storing” excess iron, making more iron available for the use of the cell. If this system is for some reason not working, this can cause some oxidative stress on the cell which leads to things like lewy bodies and synuclein. Coincidentally enough, synuclein and lewy bodies are very prevalent in PD. So now that we know iron’s role in PD, how in the world is it possible to keep iron at homeostatic levels?
Iron chelators are a way that we can do this. These chelators have the capability to decrease excess iron that is found in the cell by binding to it. Effective use of these chelators would obviously be extremely beneficial to people who are dealing with PD. As always in science, more research is needed. But, it is reassuring to me and should be to you as well that we have our hands all over this disease trying to find more and more leads to treatments and cures to one day potentially eliminate the disease.
Diabetes Evil Twin…
We hear about diabetes all the time in today’s culture. Regardless of what type of diabetes that a person has, the disease in general is much talked about in our society due to the ways that we eat. Fortunately, there are ways in which we are able to treat diabetes, as most people are aware. Unfortunately however, is the fact that we don’t realize the entire effect that the disease may have on us. Recently, my neurochemistry class read an article concerned with a potential link between type 2 diabetes and Alzheimer’s disease. No that is not a type-o but in fact the truth, this link has been indentified.
Many people are aware as to the importance of insulin in the treatment of diabetes but yet unaware, as I was, as to the role that insulin plays in your brain. Insulin-like growth factor 1, or IGF-1, is a key player in the brain as it pertains to the proliferation of cells as well as at the same time regulating the glucose metabolism that many people have come to expect from insulin.
But in the brain one of the not very well known jobs of insulin is to decrease inflammatory responses in the brain. Just like the sprained ankle that you have had before, trying to reduce the inflammation is key. If insulin is not present in the brain, or is but at too little of levels, this will increase the inflammation in the brain as well as cause an increase in oxidative stress in the brain, which can open up a whole new bag of issues. One of the issues with an increase in oxidative stress is that it leads to the apoptosis, or death, of your neuronal cells and I think just about everyone in the world knows that the death of your brain cells is a very bad thing. Low insulin also leads to low levels of norepinephrine in the brain, and this leads to an overall decrease in cognitive functioning, comparable to what we see in many neurodegenerative diseases.
This is where the link between diabetes and Alzheimer’s disease lies; it’s really a scary thought. Many people are under the impression that since we have a way to treat diabetes that it is not too big of a deal for people to live with it. But, we need to start making people more and more aware of what low insulin levels could mean. Sure, this paper that we read and this blog I’m posting is a start, but what’s even scarier is that it is just that, the start. The more we learn, the more science may keep uncovering more and more ways that diabetes is linked to a multitude of neurodegenerative diseases and conditions. We need to stay aware and make others aware that diabetes is no joke, and we definitely do not know everything about it. The importance of eating healthy has never been greater. Eat healthy people.
Should our friend Mary Jane get some credit every now and then??
Puff, Puff, Pass….
Many people associate marijuana with crime, other drugs, laziness, etc. But then why do we see a growing number of users? Why do we see states legalizing the use of marijuana for medicinal purposes? The social stigma and common associations we make need to be put on hold for the majority of this reading. So sit back, relax, and keep an open mind, as you might be surprised with what you learn.
We learned this week about the endocannabinoid system in our brain. Like all neurotransmitters and molecules in the brain, these endocannabinoids have specialized receptors in the brain that bind these molecules and produce responses in our body. These endocannabinoids can be responsible for pain relief and appetite, for example. The two endogenous endocannabinoids that are in the brain are AEA and 2-AG. Now, if you really want me to throw you for a loop then take a wild guess at what molecule is strikingly similar to AEA and 2-AG….
Believe it or not THC, the molecule that is commonly associated with the smoking of marijuana, is your answer. So what does this mean? Well, our brains contain specialized receptors that are made for molecules just like AEA, 2-AG, and THC, meaning that THC, though it is not made in the body, is also not foreign to it. So our body can handle the intake of THC, cool, but why does that mean anything?
The paper we read this week was all about how there is a plethora of science out there that supports the notion that marijuana has therapeutic effects as it binds to the same endocannabiniod receptors that AEA and 2-AG bind to. It has been shown to calm nerves, limit seizures, and even stimulate appetite in patients who need nutrition. Sure, drug companies will come up with some sort of drug at some point in our lives to deal with these same things but the scary part about those is that we don’t ever know what kind of side effects they will have. Doesn’t it at all seem odd to you that when you take a pill, you don’t fully understand what you are putting into your body or how it will affect you because it is more than likely synthetic? All I’m saying is how is marijuana worse for you than those drugs when at least marijuana is an ALL NATURAL variation of medicinal treatment. I mean it’s a plant, made in the soil of our earth, not synthesized from God knows what. If used in the correct manner marijuana doesn’t even have addictive properties so what are we waiting on? This is a chance that we don’t have very often, the chance to legalize a drug that is natural and can be used to treat a wide variety of medical conditions with minimal to no side effects and/or risk. I think our first step is to take away many of our predispositions towards the drug, take a step back, and breathe in the facts.
Join the Dopamine Craze!
Often times in college I find myself staring at a piece of paper and thinking, “huh?” I have found that this is the case for many other people as well; it’s just the nature of the beast. So, after you finish reading this post please feel free to refer back to these first two sentences, as you are not alone.
Have you ever wondered what makes your feel good, or what causes the feeling of euphoria that you get when something awesome happens to you? These feelings can be explained in the neurochemistry of your brain. The basis of neurochemistry and neurobiology centers largely on neurotransmitters and their respective receptors. Neurotransmitters are molecules that are released by nerve cells in your brain in order to transmit a signal to another cell. This cellular signaling is happening constantly in your body. It is the reason you are able to move your eyes along this page in order to read this post. It also is responsible for emotions and memory to name a few other things.
One of the most, if not the most, important neurotransmitter in your brain is called dopamine. Dopamine is very common; it is involved in your reward pathway, meaning that it is released when something good happens to you, causing a feeling of euphoria. Today however I will be discussing dopamine in a different light, we recently read an article in class that discussed the Akt/GSK3 signaling cascade. Your body has many different signaling cascades; each one of them can be seen as just a system that goes through different steps in order to produce some kind of response in your body. I know I know, at this point you might be like, “Ok that’s great and all but really why should we care what the science geek says?” Well this Akt/GSK3 signaling cascade just another way that dopamine is involved in your body. This cascade is started by the binding of dopamine to a D2 receptor, which is just a fancy name for one of the specialized receptors that dopamine has been known to bind to. Skipping all of the boring and confusing science details of the cascade I can say this: that if this cascade does not work correctly, we pay major consequences to our health.
The cascade working correctly means that there is a sufficient amount of signaling going on, but not too much or too little. Things can be thrown off if we have too high or too low of levels of dopamine in our brain. If dopamine is off, this whole system goes out of whack, and it has been shown that an out of whack Akt/GSK3 cascade can lead to conditions such as bipolar disorder, schizophrenia, and even Parkinson’s disease. Although there are many different facets to these conditions, this Akt/GSK3 cascade has given scientists potential targets for new treatments to help with these disorders. Obviously, this could lead to major medical breakthroughs. Isn’t it interesting how science takes something so small like dopamine, and relates it to something so big?
Breaking the Circle of Obesity
According to the CDC, more than one third of adults in the United States are obese. That means the annual cost of obesity in the U.S. is about 147 billion dollars (recorded in 2008). Obesity can lead to problems such as diabetes, heart disease, stroke, cancer, and, neurodegenerative diseases. Obesity has always been a concern for Americans, yet those obese have an alarmingly difficult time slimming down. I’ve often caught myself thinking this is due to little motivation; however, after reading the article Is Obesity a Brain Disease? there is a lot more to it than just not being motivated to lose weight.
Having a high fat diet (HFD) can lead to problems such as lipid peroxidation, elevated proinflammatory cytokine levels, inhibited leptin activity and more. All of these occur in the cell and can lead to even more problems, and yet another major problem with these adverse effects from a HFD is that it leads to less BDNF within the cell. BDNF is an important growth factor that helps with cognitive functioning, synaptic plasticity, and cell growth and differentiation. Low levels of BDNF can lead to cognitive decline that can be detrimental to a person’s health. But the real problem is that once these problems start it is extremely difficult to correct.
There are two important neurons that help our bodies know when it needs to eat and when it is full. They are proopiomelanocortin (POMC) neurons and agouti-related peptide (AGRP) neurons. POMC neurons release POMC when glucose levels are high and decrease appetite. These neurons are activated by insulin and leptin; thus when insulin and leptin levels are altered and not balanced POMC neurons cannot be activated and the decrease in leptin and insulin leads to the activation of the AGRP neurons. The AGRP neurons are responsible for telling the body that it needs to eat more. In order to balance these neurons the body needs a balance of leptin and insulin, but since these neurons are not the only things affected by obesity it is hard to keep this maintained.
High fat diets also lead to an increase in cytokines that are proinflammatory. Inflammation in the brain can lead to oxidative stress within the cell, which can lead to ER stress and can eventually lead to apoptosis. Proinflammatory cytokines can also lead to down-regulation of insulin secretion which can lead to decrease activation of POMC neurons along with decreasing the benefits of insulin throughout the rest of the body.
The dangers of a HFD are that just reducing proinflammatory cytokines is not good enough. There is a vicious cycle between ER stress, oxidative stress, and inflammation where each one causes the other. So how do we battle these problems? Although it may take longer than a quick fix such as liposuction or weight loss pills, exercise and healthy eating is the best way. Exercise helps with brain health and production of proteins that help fight against and clear up things like cytokines and oxidative stress. Healthy eating helps with regulating food intake and making sure that you are getting the right nutrients that will fill you up quicker with less food eaten. Although it’s simpler to just pop a pill and move on, the harder choice is the healthier choice!
Superman's Analogous Element
One of the main subjects of my education I have had the most difficulty in understanding is chemistry. It’s been one of those subjects that I’ve loved to learn about and believe it is important to understand, but have never had a “knack” at learning. Due to this, the periodic table has not become one of my closest friends. I have fought with the elements of chemistry, and they have certainly fought back. So when lithium became the topic of the week in my neurochemistry class I was far from enthused to learn about something that I’ve had a long love/hate relationship with. But, after reading the article over lithium and its uses in the medical field I have learned so much about how important this element really is.
Lithium has been used as an effective treatment for Bipolar disorder for nearly fifty years, and during that time scientists and doctors had no real idea of how or why it worked; it just did. Even now, after so many years, we are still not completely sure how lithium is able to positively affect the brain the way it does. Not only is it being used for Bipolar disorder and other mood disorders, but has also been shown to prevent and help with strokes, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease and more. In fact, when reading this paper, I came to know Lithium as the Superman of all of the elements, able to come to the rescue when the brain was in trouble.
What we know is that Lithium is able to protect neurons through multiple ways. It helps by blocking an enzyme known as glycogen synthase kinase-3, also known as GSK3. GSK3, when activated, turns on other enzymes that eventually lead to programmed cell death (also known as apoptosis), which even though the cell may not be functioning correctly, is not good. Lithium also helps with the expression of the growth factor BDNF, which helps with the survival of neurons and encourages growth and differentiation of new neurons and synapses, enhancing synaptic plasticity. It also inhibits the protein IP3, along with inhibiting NMDA receptors. IP3 can eventually lead to apoptosis, and if the cell is experiencing glutamate-induced excitotoxicity, NMDA receptor inhibition will help stop the calcium influx. Lithium also has the ability to induce autophagy within the cell by reducing intracellular inositol levels. This is done by inhibiting proteins that uptake extracellular inositol, such as IPPase, IMPase and MIT. An enhancement of autophagy within the cell is a good thing because this allows the cell to clear away unwanted proteins that may have mutated or misfolded, and thus unable to function correctly.
After reading the article about Lithium, I honestly had no idea what it couldn’t do, it just seemed so good for you! Apparently others were also thinking of it, because someone in class asked why we are not taking it as a daily supplement. One of our classmates quickly found out that Lithium, if not used as treatment, can cause nausea and other ill effects. This goes to show that we should always remember that everything is good in moderation.