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.
Crash Course on Concussions
I’ve been playing soccer since I was about five years old, and it was not until college that I experienced someone on the field get a concussion. I had always known about how they occur, and had even seen football players get concussions in high school. But I had never really known what sort of effects a concussion had on someone, nor did I really understand what concussions did to the brain until I read the scientific article The Molecular Pathophysiology of Concussive Brain Injury. I always pictured a concussion sort of like the crash dummy shown in some of the car commercials. Once you get hit, your brain sort of rocks really hard and takes a beating. But there is much more going on than just a shaken up brain.
In contact sports such as boxing, football, soccer, and hockey, concussions are quite common. When a player suffers from a concussion, the brain is hit so hard that it sort of sends everything into overdrive. The concussion causes the brain to initiate unwanted action potentials that cause an increased release of glutamate, the brains main excitatory neurotransmitter. There is also a potassium efflux, which leads to an increase in membrane pumping in the neuron. The increase in glutamate causes hyperglycolysis, and leads to the accumulation of lactate in the brain. The reason hyperglycolysis occurs is due to the brain’s ability to try and fix itself from having too much glutamate released at one time. Calcium sequestration also occurs along with mitochondrial dysfunction and oxidative phosphorylation. These occur due to the calcium influx that occurs at the same time as glutamate rushes into the neuron. Due to the mitochondrial dysfunction there is a decrease in ATP, the cell’s energy source. Lastly, due to the imbalance of calcium, glutamate, lactate and other ions within the cell, enzymes are activated that initiate apoptosis (cell death). Symptoms include headaches, nausea, dizziness, some memory loss, and even vomiting (depending on the severity of the concussion).
Although this may sound like there isn’t much to be done, measures are being taken to help protect those in contact sports from suffering from a concussion. Increased padding in helmets, head bands, and padded gloves are being required in most contact sports. This is certainly necessary since too many concussions can lead to neurodegenerative disorders such as Chronic Traumatic Encephalopathy (CTE) and dementia. CTE can also lead to other disorders such as Alzheimer’s Disease and Parkinson’s Disease.
But since contact sports are so popular, it is very unlikely that we will be able to completely prevent concussions from happening. Sometimes concussions may also happen just from falling down and hitting one’s head, or getting hit by an extremely hard snowball! So then, what is the best way to treat a concussion? A lot of rest! Doctors say that a lot of rest and little activity that could further your concussion is the best way to treat it. The severity of the concussion determines how long it may take for you to be completely recovered. So if you ever get hit a little too hard in the head, it is best to pop in your favorite trilogy (I would suggest Lord of the Rings), and sit back and relax.
So what is ALS?
Amyotrophic lateral sclerosis, more commonly referred to as ALS or Lou Gehrig’s disease was a relatively unknown topic to me until this week. ALS is a neurodegenerative disease whose end is the deterioration of motor neurons, causing loss of function to parts of the body. That’s the bigger picture anyway; there are a variety of mechanisms taking place in the pathology of this disease and in conjunction they create an extremely debilitating outcome. The main ALS story is an imbalance of calcium in different areas of the cell and the outcomes that this leads to. Namely the cytosol, mitochondria, and endoplasmic reticulum were discussed this week. The imbalance of calcium leads to a myriad of inconvenient outcomes, including protein misfolding and accumulation, as well as oxidative stress.
The symptoms of this disease are quite extensive and can make life extremely difficult for patients. Being that motor neurons are affected, bodily motion becomes exceedingly more challenging as the disease progresses. In the early stages muscle weakness and stiffness are common, accompanied by fatigue, poor balance, and other symptoms. The middle stage is characterized by some muscle paralysis and further weakening of others, as well as trouble swallowing and weakening of respiratory muscles. Late stages are characterized by paralysis of most voluntary muscles, extreme difficulty breathing, very limited mobility, impaired speech, and inability to eat or drink through the mouth. Since the respiratory system is so severely affected, this usually leads to death due to inability to properly breathe or swallow.
The intriguing part about this disease is that no one really knows how it is caused. Only about 10% of cases are hereditary, the rest are sporadic. There is no way of reversing the disease, but the drug riluzole was developed which helps counteract the disease. Riluzole decreases glutamate release in the brain which decreases motor neuron death, thereby extending the life of the remaining functional neurons.
This disease was made famous by the baseball player Lou Gehrig, hence the name. In recent years however, there has been some controversy over this, as it turns out that Gehrig might not have had ALS at all. In fact, many professional athletes may have been falsely diagnosed with ALS in the past, when they actually had a completely different disease. Chronic traumatic encephalopathy (CTE) is characterized by the same symptoms as ALS, but is caused by multiple brain traumas or concussions. Before CTE was discovered, athletes that received many concussions in their career were diagnosed with ALS. It is hypothesized that CTE might be under the “ALS umbrella” of disorders, as it is characterized by the build up of the same proteins in cells.
ALS is a nasty disease, no question about it. The real question is, what more can be done? In our discussion this week our professor brought up a good point: Do people really know that much about ALS? Do you think if people knew more about it, more money would be given towards research for a cure? Personally I didn’t know very much at all about ALS before this week, and I think that if people were more aware about how horrible and debilitating the disease can be, more work would be done towards finding a cure. Hopefully our blogs from this week will spread some awareness and make a small impact in the path towards a cure.
Looking Past the Intimidation Factor of a Capstone Course
This fall I had the opportunity to take neurochemistry, both for my neuroscience minor as well as for the Capstone requirement for my core. When I signed up, I really had no idea what a Capstone was supposed to be; to me it just sounded like a sort of academic “cherry on top.” I have to say, it has been more than just something sweet, meant to sweeten the deal or look good on a transcript. This semester has been a great interdisciplinary experience, which would not have been complete without neurochemistry. Before I talk about my experience this semester, I would like briefly explain the structure of the class. During the first three weeks, we covered basic information that laid the groundwork for the rest of the course. For the duration of the course, each week was devoted to covering a specific topic such as obesity, diabetes and Alzheimer’s disease, concussions, Parkinson’s disease, or endocannabinoids. One of the most interesting, yet challenging parts of these papers was their recent publishing. All of the research we used was published within the last three years, making our course material extremely relevant to developments in the world of medicine. During the first day of class for the week, we would cover the basics of the assigned article. On the second day, we would cover topics mentioned in the paper or related to the issue at hand that we wanted to learn more about. Last, we would have a discussion on the paper and related topics and try to relate the information to society at large.
I was really nervous to start classes and get into the swing of things this semester, and for good reason as Neurochemistry, integrated Anatomy and Physiology, and Drugs and Behavior proved to be a challenging combination, taking many hours out of my already abysmal sleep schedule. Despite sacrifices in leisure time and REM sleep, I can safely say I enjoyed my material this semester more than any other. I was very enthused by the physiology of the body, how substances are absorbed, their pharmacological profiles, effects on behavior, and the neurochemical correlates behind said behaviors. The intimidating course load I took on this semester turned out to be one of the most rewarding interdisciplinary experiences I could ask for, especially during discussions; I did not expect sociology to complement any of my other classes and was pleasantly surprised to discover the information learned there allowed me to speak about healthcare on a broader scale, examine both biological and social phenomena, and thereby enhance my own experience in the discussion portion of the class.
At the beginning, our class was told that we would get out what we put into the class. For me, this ended up being very close to the truth. Going into the class, I already had a passion for neuroscience as I one day wish to pursue a career in medicine pertaining specifically to the brain in some way. I was able to learn about things that I was interested in from the articles themselves and further explore these interests with the related topics we presented each week. The integrative type of learning encouraged in this class is not implemented often enough in the academic world; it feels so bittersweet that I only got to experience this at the end of my undergraduate career. Concluding, I would just like to say I am a huge proponent of interdisciplinary learning; after quizzes, tests, presentations, and other academic evaluations are no longer present, informational boundaries are blurred by the applications of this knowledge. Medical innovation for innovation’s sake is intriguing, but these emerging products and procedures must be relevant to the needs of the world and safe for use, not to mention practical. Dissemination of information regarding new discoveries and subsequent integration of new technology or procedures into everyday life requires a broad understanding the many facets of organization, including entrepreneurial ventures, corporations, societal needs, or governmental regulation. I am therefore more than satisfied with my experience this fall and hope many others receive similar opportunities.