Disease/Health

I think you were dropped on your head as a child.

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Concussion "basics"
Concussion “basics”
Source:http://www.maafirm.com/library/dallas-fort-worth-concussion-injury-lawyer.cfm

What is the real meaning behind this common saying? Usually, this saying is used when a person says or does something that isn’t very intelligent. The rationale behind this statement is that the hit to the head of a child is likely to cause brain damage, likely through a concussion. Concussions are becoming increasingly scary to the general public as more research is able to demonstrate their negative long-lasting effects, as demonstrated in the article The Molecular Pathophysiology of Concussive Brain Injury.  

                The problem with concussions is that many times, people are unaware they even had one. There are different intensity levels of concussion, ranging from minor headache and grogginess, to entire loss of consciousness. If someone experiences a minor concussion, it is possible that they won’t realize it could have serious consequences. The other problem facing concussion is that physical contact sports, like football and hockey, are becoming increasingly more intense and rough for both males and females of all ages. Return to play policies seem to be on qualitative evaluation of symptoms rather than quantative measurements of brain health or recovery.  Experiencing multiple concussions in a row greatly increases the chance for long-lasting, severe damage. But if healing occurs between concussions, the risk is much lower.

                Most people understand that a concussion occurs from a hit to the head. The hit could be from a sport, falling, car accident, or really anything that causes the brain to crash into the skull. When this happens, brain cells become damaged. The membranes become permeable to many ions. This causes nonspecific depolarization of the cells, which leads to random action potentials firing. This causes the release of neurotransmitters which excite other molecules. This excitation causes an overabundance of potassium to rush into the cell. This causes the ion pumps in the cell membrane to work extremely hard to restore the cell to its normal condition. This requires an extreme amount of energy in the form of ATP. In order to compensate for the extreme energy need, the brain goes into hyperglycolysis mode. This means the cell is taking glucose through glycolysis, breaking it down into two molecules of pyruvate, and then into lactate and ATP. The ATP is used by the brain, but the lactate builds up in the brain as lactic acid. This is unfortunate because the buildup of acid in the brain is quite detrimental. Next in the process, calcium influx occurs which causes the oxidative metabolism in mitochondria to become impaired. The mitochondria are then unable to produce enough ATP for the brain, which leads to a decrease of available energy. This activated calpain and apoptosis, or cell death.

                The axons of neurons in brain also experience extreme negative side effects as the result of a concussion. The axolemma responds negatively to the previously described calcium influx by disrupting its normal behavior. Its neurofilaments become compacted due to phosphorylation or cleavage of the sidearm chains. This causes the axonal organelles to accumulate as the microtubules of the axon begin to aggregate. All this disruption leads to severe swelling of the axon and eventual death.

                Continuous cell and axon death in the brain can lead to long-term damage. Unfortunately, no real medical or pharmacological treatments for concussions are available. The best, and essentially only, treatment for a concussion is rest and minimizing brain usage. Students shouldn’t attend school or attempt homework until they are symptom-free for at least 24 hours. This is a harsh reality to face since concussive symptoms can last for weeks. For high school students, this might be a huge problem, but to a college science student, missing weeks of school could mean the necessity of repeating classes and potentially not graduating on time and paying for an extra semester, likely without financial aid. This may seem like an extreme consequence, but it is a very real scenario. Missing a month of college science classes would be terribly hard to learn on your own, plus you can’t even keep up with the work while you are out sick because studying causes the brain to work too much during recovery. As for athletes, missing a month of practice could also be career ending. Most coaches wouldn’t allow a person to play after missing a month of practice. Plus, a month of staying in bed as much as possible is likely to lead to loss of muscle mass.

                If concussions can have such serious negative effects, effecting both physiology and life style, what can be done to prevent them? Helmets are an obvious, but they can’t protect everyone at all times. Even state of the art helmets lead to concussions in the NFL and other professional athletic leagues. What about people who experience concussions in everyday life from slipping on ice or falling off a ladder? In that case, education on the essential resting period after a concussion is the best medicine. People need to realize the extreme effects that are consequential of improper concussion treatment. Too early return to play, school, or regular brain function can increase the risk of experiencing an additional concussion. There is a terrible period of brain vulnerability after concussion. It is also nearly impossible to turn off brain function, so the healing process is consequently slowed down.

                The most important things to gain from this specific article are: The mechanism of concussive brain damage, the negative long-lasting effects of concussion (ex. Dementia like symptoms), and the importance of healing and prevention of further concussions. Hopefully, this article leads to thoughts and conversations as to which types of activities that leads to concussions outweigh the possible brain defects that can come from them. Conversations and brainstorming ways to properly deal with concussion are necessary for all people since concussions can happen to anyone.

Disease/Health

Iron and Parkinson's Disease: Why We Should Keep Our Bodies Balanced

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Which areas in the body are vulnerable to iron overload?

Two weeks ago in class, we talked about the importance of iron levels in the development and progression of Parkinson’s disease. As most of the public knows, Parkinson’s is a movement disorder that is characterized by muscle weakness as well as rigidity. As the disease involves a process of progressive neurodegeneration, resulting in concomitant worsening of symptoms, research in preventing damage at the earliest possible stage of disease has been of utmost importance. But where does iron come into the picture? Well, some recent findings have pointed to the role of iron homeostasis, or rather the alteration thereof, in the initiation of the cascade of events leading to Parkinson’s pathology. Iron is a very important element in the human body as it serves as a co-factor and electron carrier in many reactions; a great example of this is hemoglobin function. Iron also plays a role in cellular metabolic processes and is therefore of utmost importance in every area of the body, but we’ll focus on the brain. A significant increase in brain iron levels of Parkinson’s patients. Generally, iron accumulates in the brain over time, but its concentration is balanced by the action of several proteins. An imbalance of iron in the brain can lead to larger amounts of free radicals and subsequent reactive oxygen species in the brain. Free radicals cause a protein called α-synuclein to aggregate, leading to a cascade of events that result in cell death. This cellular mishap is accelerated by increased levels of iron which stabilizes the α-synuclein aggregates and even leads to increased expression of the protein.
Given these findings, it would be therapeutic for treatments to target this iron imbalance in its early stages to prevent the progression of symptoms. Iron-chelating drugs are currently being developed by independent researchers and pharmaceutical companies with some success in halting neurotoxicity. One very interesting finding is that a major catechin protein in green tea, called (-)-epigallocatechin 3 gallate or EGCG for short, has shown highly potent ability to prevent neuronal death by scavenging reactive oxygen species as well as binding/chelating excess iron to form an inactive complex.
How should the average citizen use this information? Given oxidized species build up in the body over time due to declining antioxidant activity, it would be very beneficial to combat this and prevent the buildup of potentially dangerous chemicals in our bodies before they become a problem. Some research suggests that products containing antioxidants possess a fair amount of value. Others state that simple remedies such as green tea hold very little clinical value. Either way, the average person doesn’t have much to lose by switching out coffee for green tea once in a while.

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A Shift in the Perspective on Endocannabinoids and Marijuana

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According to the United Nations Office on Drugs and Crime, marijuana is the most-used illicit drug in the world.  In the United States, it is classified as a Schedule I  drug, which is defined as “a substance or chemical which has no currently accepted medical use and a high potential abuse.”  These are considered to be the most dangerous drugs, and a user is severely at risk for psychological or physical dependence.  Marijuana is joined on this list by other substances such as heroin and ecstasy.  Schedule II drugs are also relatively dangerous, but are considered to carry less potential for abuse than the schedule I drugs.  A few examples from this list include cocaine, methamphetamine, and oxycodone. (For more information, see http://www.justice.gov/dea/druginfo/ds.shtml)
If one takes a look at the current marijuana use laws across the country, or even just takes a second to listen to those arguing in the popular debate, it is easy to see that the legal classification of marijuana as a Schedule I drug with “no currently accepted medical use” is somewhat out of line with the twenty states that currently allow marijuana for medical use.  Though federal law still prohibits its use, the Department of Justice has announced that as long as those states which have legalized it for recreational use regulate it tightly, it will not challenge the laws in Colorado and Washington at this time.  (http://www.justice.gov/opa/pr/2013/August/13-opa-974.html)
The American public has historically been opposed  to the legalization of Marijuana, but a recent Gallup poll shows that for the first time, a majority of Americans are in favor of legalizing Marijuana.

I have always been on the fence regarding the legalization of marijuana, even for medical purposes.   However, after reading an article recently regarding the biochemistry of the endogenous cannabinoids (substances made in the body which bind to the same receptors that the active substances in marijuana do), my opinion has changed.  There are many different mechanisms and pathways by which the substances in the endocannabinoids may act, and these may be useful targets in the treatment of certain conditions.  For instance, endocannabinoids are involved in vasodilation, which might be important in the treatment of high blood pressure.  They can also mediate the effects of pain and inflammation.  Perhaps the most surprising actions to me were those that targeted the treatment of cancer both directly and indirectly.  The binding of anandamide and 2-arachidonoylglycerol  (two substances found in marijuana) to the CB1 receptor in the body can induce apoptosis, or programmed cell death, which is essentially the goal in treating many types of cancer.  Indirectly, substances in marijuana can also play a role in the treatment of cancer as well.  Often, those undergoing chemotherapy for the treatment of cancer experience a loss of appetite, and substances in marijuana can help to induce someone to have an appetite.  This can also be useful in treating anorexia.
Of course, we still cannot completely ignore the more harmful effects marijuana exhibits.  There are certainly issues like the potential for addiction which caused it to be classified as a Schedule I drug in the first place.  However, after learning of all the potential medical uses for marijuana, I cannot help but think that we need to rethink its classification as a Schedule I drug with  “no currently accepted medical use.”

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Iron Overload

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I have always viewed Parkinson’s disease as something that only effected a person’s movements. After this week, I have learned that it effects to much more than that. There are many differences in the brain from a person who has Parkinson’s disease, and a person who does not.
 
Parkinson’s disease is characterized mainly by the loss of dopaminergic neurons, and the formation of Lewy bodies that reside in the remaining dopaminergic neurons.   These Lewy bodies replace other elements within cells. Lewy bodies are not the only disruption in cells that a person with Parkinson’s disease has; there are also neurofibrillary tangles (NFTs) present within PD patients. NFTs and Lewy bodies are very representative of PD patients, but it was interesting to learn that the amount of iron in people with PD is significantly higher than people who do not have PD.
This raised an interesting question: does the food a person eats play into the likelihood he or she will develop PD? As a class, there have been many topics that relate neurological disease to the food that is put into our body.  The relation with type 2 diabetes and Alzheimer’s disease, as well as green tea being extremely beneficial to PD patients in helping reduce oxidative stress, thus increasing the amount of properly working biological functions, has shown that what we feed ourselves may have a drastic effect on our brain’s health.

Although it should be no surprise, it is still fascinating that what we eat really does determine how healthy we are, both physically and mentally. Food and water are the resource for most of the functions our body conducts.  As time has gone forward, we have discovered that food is an important factor in our livelihood, but it takes a lot of effort to eat what our body truly needs, as well as being able to afford it. With this dilemma, companies have capitalized by selling pills, tablets, etc. to keep a person at optimal health without having to worry about what else is being put into his or her body.
This relates back to Parkinson’s disease in that those with PD have a much higher concentration of iron than those who do not have PD; is this due to an individual’s diet? There have been many studies conducted showing the benefits of a Mediterranean diet or an Oriental diet (a real Oriental diet, not one consisting of deep fried chicken smeared in some sugary sauce—it is delicious, but not very comparable to what is actually eaten in the Orient) compared to a typical diet of those who live in the United States.
 
The amount of red meat a person in the United States is extraordinary.  This could result in a high concentration of iron in the brain, thus being an influence on developing Parkinson’s disease. It is probably not going to fix the problem entirely if people change the way they eat, but it could be beneficial, just as drinking green tea has been shown to do.

Health/Hot topics

"Light it up and Take a Puff, Pass it to me Now"

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For years marijuana has been used both medicinallly as well as recriationally. These days society has made a huge commotion about this drug, trying to determine if it is an “okay” thing to allow people to use. There is plenty of evidence to suggest that this drug is being used more and more frequently whether it is legal or not. For instance a lot of artists, espcially in the rap and hip hop industry, have used references to marijuana use in their songs. These songs are being listened to everyday by millions of people. Often times the main listeners of this music are impressionable young children or young adults. This makes me wonder what kind of impact this is having on the youth of America in whether or not they are using marijuana. Not only that but why are people using the product; is it because getting high is cool and fun,  or could it actually help these younger people feel more calm, get more sleep, eat better, etc.? I think this is why it is such a hot topic and why some states have decided to legalize this drug where others say it is too dangerious or unhealthy to allow.
Since the use of marijuana in the United States is such a controversial issue, have you ever found yourself asking why? or what makes a plant, of all things, something to argue over? If you have, you may want to first understand what makes this plant a drug. Endocannabinoids were the topic our neurochemistry class discussed this week by reading and anylizing the article “Endogenous cannabinoids revisited: A biochemistry perspective”. We discovered that the plant Cannabis sativa (marijuana) contains more than 400 chemical components, 60 of which belong to the cannabinoid class. Recently the main cannabinoid psychoactive component in marijuana was discovered. This is what we know as THC. THC does produce many psyhoactive effects in ones brain. Research has found that these cannibinoids act on the CB-1 and CB-2 receptors in our brain causing a person to feel “high”. Although this is largely frowned upon, recent research has been focussing on how the chemical components in marijuana may be more beneficial than harmful if used properly. For example we discussed that one study found that a certain strain of the drug, that had lower THC levels, can be used to treat people with epilepsy. The reason that a strain like this works better than other strains is becuse there is a cannibinoid called cannibidol in marijuana that is linked with health benefits and is less psychoactive than the THC. By consuming a strain that has less THC and more cannibidol in it, a perosn would have reduced psychoactive effects and possibly have more health benefits from the drug. There is a lot of research going on today that is trying to find out how using cannibinoids in different treatments would work and how they would be beneficial to society. Treatments for a lot of things are blossoming such as: treating cancer and cancer symptoms, helping with eating disorders, slowing down the effects and controlling the symptoms of HIV and AIDS, helping with depression, reducing headaches, and aiding in many pain disorders. I think people warm up to this idea because it is a “natural” solution to very difficult problems we face in the health problems we are experienceing today. A lot more research needs to be conducted in order to pinpoint specific treatments using endocannibinoids, cannibinoid receptors, etc. however, I  do think scientists are going in the right direction to discover how marijuana can be considered a treatment not just a drug.

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The significance of the Atk-GSK3 pathway

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Of the countless neurotransmitters associated with the human central nervous system, dopamine is perhaps one of the most crucial neurotransmitters to understand in its pathways and signaling. Dopamine is utilized in a variety of different regions of the central nervous system, including cognition, locomotion, and emotional behaviors.
The regulation of dopamine is crucial to the well being of human health. As soon as the pathways that govern dopamine signaling, uptake, and various other aspects of its existence in the central nervous system start to get out of whack, things can start heading downhill pretty quickly.
Given the complexity and variability of dopamine pathways and signaling, it is absolutely miraculous that dopamine-related disorders aren’t more common. There are many different signaling pathways that each contain different chemical interactions that illicit responses. Specifically, the Atk-GSK3 pathway is of great importance. Disruptions in this pathway have been linked to the development of disorders such as schizophrenia, bi-polar disorder, depression, Parkinson’s disease, and many others.
In the grand scheme of things, chemical reactions occurring at the molecular level seem minuscule compared to the implications that arise from a disease like Parkinson’s or schizophrenia. However, if we wish to treat these disorders to the best of our ability, we need to focus on the underlying mechanisms that produce the effects we see. Completely understanding these pathways will hopefully allow us to treat these disorders in the most optimal way and possibly even provide methods of curing diseases that have previously been incurable. Research continues to uncover more and more information about dopamine and other important neurotransmitters, and it is crucial that we keep funding and supporting this type of research.

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As natural as it get

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We recently read an article about endocannabinoids. Yes, cannabinoids just like the active ingredient in marijuana, THC, or tetrahydrocannabinol. The part of the article that was most intriguing to me was the fact that these chemicals are completely natural in our body, as in we make them. Endocannabinoids act like a relay system in our body. Our neurotransmitters are released and bind post-synaptic neurons, which releases endocannabinoids. This tells the pre-synaptic neuron to stop releasing neurotransmitters. THC has a similar effect on the body. Here is where our discussions got interesting. THC acts exactly like a chemical our body already produces but has a huge stigma around it. Because of this stigma, one of the potentially beneficial parts of marijuana, cannabidiol, is often forgotten about. Cannabidiol is another cannabinoid, so it acts like the ones our body produces and THC. However, cannabidiol is far less psychoactive than THC. Cannabidiol is the part of marijuana that is often linked with the positive effects, such as preventing tumors and stopping seizures. In fact, a fairly recent article on CNN talked about how a specific strain of marijuana that was high in cannabidiol and low in THC was used to treat a girl with Davet’s Syndrome, a severe version of epilepsy. So we have natural endocannabiniods and cannabidiol that are generally helpful, but THC is the most commonly heard of and causes a lot of stigma for all cannabiniods. I wonder were the stigma came from in the first place. It does make you think, we have these chemicals are body uses for regulation that are also found in a plant. Some people use the plant to get high, others use it for health benefits. Should we be utilizing this plant, even though it is illegal now? Who knows, but cannabinoids are an interesting chemical nonetheless.

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Akt, Gsk, Dopamine and how they can fix your brain

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The other week in class we discussed the Akt/Gsk pathway and Dopamine receptors. To put it lightly the article we read was dense. Through all the scientific language and technical terms one general idea stood out. Your body releases dopamine, dopamine binds these receptors, and the receptors keep Akt inactive so Gsk can remain active and cause cellular responses. As exciting as that all sounds what does it matter? Well dopamine is one of the most important neurotransmitters in the brain and these proteins play a major role in its signaling pathway. Research is currently investigating the role of these signaling proteins in psychological disorders such as Bipolar and Schizophrenia. The antipsychotics we use now are effective but come with harsh side-effects. This is because these pharmaceuticals typically block dopamine receptors and while this works to stop the psychological problems, it causes a widespread effect on the body. The hope is that the issue with psychological disorders is that maybe the problem lies farther downstream from the dopamine receptor in the Akt/Gsk pathway. If we can find a protein or something that is causing the problem and can find a way to fix it we can hopefully manage psychological disorders without affecting something as major as dopamine receptors. This is easier said than done. The kind of research it takes to find what protein is causing the issue and figuring out a way to fix it costs huge amounts of money and takes a lot of time. But, nonetheless, the important of the Akt/Gsk pathway in the body cannot be undervalued. Some day it may lead to a better antipsychotic drug, or just a better understanding of dopamine.

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Should we puff puff pass on the use of cannabinoids?

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Despite its legal status, the use of marijuana is not uncommon. In fact, it is the most commonly used illegal drug in our society. In addition to its recreational use, marijuana has been used medically for hundreds of years. Although the use of marijuana might not be new, finding out how it works has just begun. This week in neurochem we discussed the article “Endogenous cannabinoids revisited: A biochemistry perspective.” As we discussed the intricacies of marijuana, THC, endocannabinoids and their receptors, it became apparent that THC and its natural analogues may be more beneficial than they are harmful.
The first step to understanding the benefits that cannabinoids can have comes through understanding how they work. The cannabinoid receptors were first discovered when researchers started looking into how THC and marijuana work in the body. They discovered certain receptors on cell membranes that specifically bind THC. As research continued, scientists discovered molecules that are naturally produced in your body that also bind these receptors. The most common of these molecules are known as 2-AG and AEA. The receptors are known as the CB-1 and CB-2 receptors. As research continues, more endogenous cannabinoids have been suggested as well as at least one more receptor type.
So what are the benefits that can be caused by cannabinoids? Medical marijuana has been used for Cancer, HIV/AIDS, multiple sclerosis, anorexia, anxiety, depression, and numerous other illnesses and conditions. In addition, it has been shown to have anti-proliferative and analgesic effects. In addition to the use of medical marijuana, researchers have been studying analogues of THC, the primary active compound found in marijuana. One of the most promising compounds is known as cannabidiol. Cannabidiol is second only to THC in the marijuana plant in terms of presence. It has been shown to have less psychoactive effects and may have more medical benefits than THC. Currently, a large amount of research is focused on cannabidiol in order to better understand how it works and the benefits it may have.
With the noted benefits of cannabinoids, the question then arises of how we should approach this knowledge. Although the use of marijuana is largely prohibited, its use may be beneficial in the treatment of a variety of neurodegenerative diseases. In addition, cannabinoids seem to alleviate a wide variety of problems without the side-effects of many pharmaceuticals. Cannabinoids might just be the answer to improvement of treatment for a variety of diseases; the knowledge we do have points to the positive effects that cannabinoids can have. So should we just take this knowledge and run with it? Although I can see and understand the benefits that cannabinoids can have, I think it is important that more research is done prior to widespread use. In addition, if marijuana or other cannabinoids are used for treatment, it is important that they are properly monitored by a physician as with any other medication. With proper research and monitoring, cannabinoids seem to be a promising treatment for a variety of disorders and diseases.

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Iron: More than a Metal

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Parkinson’s disease (PD) is a disease in which dopamanergic neurons experience substantial damage and even death. It affects 1-2% of people overage the age of 60, affecting more men than women. The causes of PD have typically been associated with oxidative stress and other toxic actions which lead to the build up of Lewy bodies in the brain which lead to death of neurons. A new study entitled, Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators, discusses the effect that iron might play in PD. One of the interesting things about this article is that it is able to supplement theories that are already in place about PD with a new idea. It doesn’t discount any of the old information about PD, but it adds a new piece to the puzzle that could help solve the problem.
Brain-iron homeostasis is regulated by interaction between two types of cells in the brain called endothelial cells and astrocytes. It is also regulated by two proteins called IPR1 and IPR2. These proteins help to regulate the amount of each type of iron in the brain. In the body, iron can take on two forms: one with a charge of +2 and one with a charge of +3. It is important to keep these two types of iron regulated because dysregulation of these two ions has been visible in PD. Too much iron in the brain has been studied and been shown to lead to PD, Alzheimer’s disease, and Multiple Sclerosis. Iron is important for the brain because it used to either reduce or oxidize molecules. Improper oxidation or reduction can lead to problems.
Like mentioned before, dysregulation of iron +2 and iron +3 has been seen in the brains of PD patients. One specific problem this causes in PD is the aggregation of alpha-synucleuin proteins due to iron radical molecules in the brain to form Lewy bodies. These Lewy bodies lead to death of neurons. One way this paper talked about treating the iron dysregulation is with iron chelators. Iron chelators are molecules which bind to iron and then remove it from the body. Iron chelators are therapeutic because they have antioxidant effects, prevent alpha-synucleuin aggregation, and can stabilize HIF (a molecule that is used to regulate transcription).
PD might not be as “hot” of a topic in terms of neurological disorders compared to others, but it still important to try to understand where it comes from and how it can be prevented and treated. Some people may feel disconnected from PD since it affects only a small part of the population. Further research into the mechanisms of PD could also bring about conclusions about other neurological disorders as well.
Since PD is diagnosed later in life, I think it may people don’t think much about preventing it. But, in my opinion, prevention is the best way to deal wit disease since it possibly alleviates having to treat the disease in the future. With the iron part of the PD story, it can be difficult since many women struggle with anemia. When trying to eat an iron-rich diet to control anemia, it would be unfortunate to develop PD as a consequence.
For people without anemia, in order to prevent PD it seems it would be important to eat a sufficient amount of iron to stay healthy, but keep the excess amount as low as possible.
The article also spoke about the positive effects of green tea in terms of PD. If this fact were made more public, it could be possible to help prevent/treat PD with the simple treatment of drinking or supplementation of green tea.

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