The topic of discussion in class this week was concussions as we dove into the article “The molecular Pathophysiology of Concussive Brain Injury.” Before we even began to consider the scientific aspects of concussion, I first paused to consider how prevalent concussions are today. It is almost certain that an individual or somebody that they know have had at least one concussion in their lifetime. According to the paper, approximately 1.6 to 3.8 million athletes suffer from a concussion each year. Also known as mild traumatic brain injury, concussions drastically alter brain function. So why is it that concussions have become so common? Have we become apathetic to their effects, focusing rather on the pleasure we gain from sports? What measures should we take to better protect from and screen for concussions? While we certainly did not answer all of these questions as a class, we did discuss some interesting ideas.
In addressing concussions, it is important to first understand the mechanism by which they occur. A concussion is initiated by a mechanical trauma. This trauma causes the neuronal cell membranes to be disrupted and axons to stretch, allowing for ions to freely flow. Indiscriminant ion flow allows for the disruption of many cellular processes (nonspecific depolarization, release of excitatory neurotransmitters, potassium efflux, increased activity of membrane ionic pumps, hyperglycolysis, lactate accumulation, calcium influx, decreased ATP production, initiation of apoptosis). Although the exact mechanism may not be interesting to everybody, the most important thing to understand is that the cells of the brain are firing at random, working extra hard, using extra energy, and may be damaged beyond repair.
Symptoms of a concussion include behavioral changes, memory and attention impairment, headache, and unsteadiness, among many other possible symptoms. Early on, an individual can expect to suffer from headaches, dizziness, nausea, vomiting, and lack of awareness. As time progresses, individuals can suffer from persistent headaches, sleep disturbance, diminished concentration and attention, memory dysfunction, and lack of awareness. Depending on the severity of the trauma, severe brain injury can be sustained. In terms of treating a concussion, there’s not much that can be done. It is imperative that an individual suffering from a concussion takes the time to allow his or her body to heal. This includes proper rest, not engaging in strenuous activity (both physical and mental) and eating a nutrient rich diet. Some research has shown that a ketogenic diet may be the best diet after a concussion has been sustained. Ketone bodies have been found to improve mitochondrial function as well as regulate the expression of genes related to apoptosis, inflammation, neurotrophins and molecular chaperones.
With the effects of a concussion being so clear, are we taking the proper precautions to prevent them? The NFL has been taking steps to decrease the incidence of riskier hits, including stronger enforcement of helmet to helmet collisions. While this is great, should we be doing more? I am by no means an expert on the topic, but I still think there are improvements that can be made. One of the biggest topics of our discussion was how concussions are handled in college. While it is important that students have the proper amount of time to rest and heal, the rate at which college classes move makes it nearly impossible to return to the classroom after a concussion. With many student athletes at Concordia, this could drastically affect their college career. We discussed the need to implement a system that aids students that have suffered a concussion so that they may more easily return to the classroom. While I certainly do not have the answers to this problem, I believe it is important that better screening is implemented to check for concussions. In addition, I believe it is important to allow for proper healing time. By making some changes in how concussions are handled, hopefully we will be able to decrease the incidence of lasting brain damage.
Dopamine and the Akt/GSK3 Pathway
If there is one thing I’ve learned after reading scientific articles it is that there is always something more I need to learn. Especially after reading the article “Beyond cAMP: The regulation of Akt and GSK3 by Dopamine Receptors”. The article was so thick it was like swimming in a pool of jell-o. But luckily, with some handy tips that my science classes have taught me throughout my years at Concordia, I’ve learned that the only way to eat an elephant is one bite at a time.
Recently, my neurochemistry class read an article about the importance of dopamine and its receptors within a signaling pathway called the Akt/GSK3 pathway. This pathway is involved in all sorts of things such as glucose metabolism, apoptosis, and cell proliferation, transcription and migration.
There are many different kinds of receptors, and the ones most important within the Akt/GSK pathway are the D2 receptors. D2 receptors are a sub family of the dopamine receptors that activate other molecules that eventually inhibit the production of cAMP, an important second messenger molecule involved in many biological processes, and inhibit Akt phosphorylation of GSK3.
Once the D2 receptors are activated, they also inhibit the activation of Akt kinase, which allows the GSK3 kinase to proceed. This is done by the D2 receptors activating a complex, or group of molecules, to form together. This inhibits Akt activation, which means Akt cannot phosphorylate and causes GSK3 to activate.
In certain mood disorders, such as schizophrenia and bipolar disorder, there is an imbalance of dopamine within the brain. Many antipsychotic drugs are used to help this imbalance by working through the Akt/GSK3 pathway. These drugs act as antagonists on the D2 receptors, which causes an increase in Akt activation by not allowing the formation of the inhibitory complex, which in turn decreases GSK3 activity. Thus, too much activation of GSK3 can lead to negative side effects and have been seen to be a possible cause for these disorders.
It’s a lot to understand, especially after tearing the article apart only to simplify it to knowing simple mechanisms when there is so much more going on. But one thing is for sure, the brain is complex and there is always more to learn about it!
Why are Men more likely to get Parkinson’s disease?
Parkinson’s disease is a degenerative disorder of the central nervous system. The symptoms are caused by the death of dopamine generating cells in the brain. Symptoms of the disease are shaking, rigidity, and movement along with mental symptoms such as thinking and dementia. Resent research shows that men are more likely to get the disease than women. The question is why does this occur? One reason behind this is due to the different life styles between the genders. Men tend to have jobs that expose them to toxic chemicals which have been linked to causing PD. MPTP is a chemical which has been shown to cause Parkinson’s like symptoms and is now used to cause the disease in rats for testing. Men are also more likely to get a head injury severe enough to cause damage which later on could lead to PD. Another fact could be the types of hormones men and women produce. Research has shown estrogen may have protective effects against the formation of the disease. Men tend to have a higher level of iron in their body than women. This is a problem because research shows that the accumulation of iron in the brain is another possible factor for PD. However, the research at this time is inconclusive if this maybe another factor to why men are more like to develop PD.
Concussions and their effects on sports
Concussions or mild traumatic brain injury (mTBI) is a head injury that consists of temporary loss of brain function. Symptoms can manifest in a variety of physical, cognitive and emotional. A person whole receives an mTBI can show signs of temporary motor loss, memory loss and in some causes mood changes such as depression. To this day the best treatment for mTBIs is still to get plenty of rest and avoid physical and mental excursion like sports and school. 1.6-3.8 million athletes suffer from concussions yearly. These concussions are most commonly found in contact sports like football and boxing. Due to the serious nature of these injuries many have questioned the actions in these sports. Football on all levels has been brought under the microscope on this topic extensively in the last decade. Before this football has had an almost violent nature to it. Some would even say there was even a promotion of this violent nature by certain parties and individuals. However, the cover ups about the long term effects of concussions could no longer stay hidden which is why most recently those parties and individuals have changed them game. Main rules have changed to reduce the number of concussions all the way from little league to the NFL. However, some of these changes have made some parts of the game worthless. Most noticeable is the kick off in football. The caliber of kickers in the NFL are so high that main of them can kick the ball out the back of the end-zone without even trying. This simple change of moving the football up 5 yards practically eliminates the kick off as a whole. It has also eliminated a lot of big hits from the game even though some are just good defensive tackles. The fear of being ejected or fined for performing well dwells in the back of players mines. This is not saying that these rules do not have their place in the game. The main reason for they are there is to insure the safe of the players, but how far is too far? Has safety gone too far already or has it not gone far enough? These are the big questions that have not been answered yet.
Dazed and confused: where should we stand on medicinal marijuana?
“I swear officer, that’s not mine” seems to invoke the image of some punk teenager getting busted with pot or perhaps a scene from the movie Pineapple Express (pictured above). That image also usually carries a certain stigma with it. I would say this stigma is certainly warranted, but what if marijuana could be used in a healthy fashion? Could rolling up a doobie from time to time really improve your health?
This last week we explored a review article on the endocannabinoid system, Endogenous cannabinoids revisited: A biochemistry perspective. I had always heard that marijuana had medicinal uses, but I had never really known what those were or how much truth they held.
The human body produces two primary endogenous cannabinoids: anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They are modulators of a variety of physiological functions throughout a diverse array of systems in the body, including the central and autonomic nervous system, the immune system, endocrine network, and reproductive system. They are involved in anti-inflammatory actions, analgesia, and feeding behavior, as well as a number of other biological effects.
Now for the interesting part: marijuana contains a cannabinoid called tetrahydrocannabinol, or THC for short. This is the chemical that is primarily responsible for the psychoactive effects that an individual experiences after smoking marijuana. It binds to the same receptor that AEA and 2-AG bind to and consequently produces many of the same effects, especially analgesia and altered feeding behavior, also known as “the munchies.” Extensive research has been carried out to assess the question as to whether or not marijuana holds any medicinal value, and the results suggest there are many practical uses for it. Recent evidence suggests that THC may play a helpful role in the control of cell death/survival. Among other uses, marijuana has been shown to be tremendously beneficial to those who suffer from chronic pain.
Whether or not marijuana had medicinal value is not the question. It does, and there is very little evidence against its practicality and usefulness in a variety of different areas of medicine. The question is how to go about deciding whether or not to use it for medicinal purposes. If there is an abundance of positive uses of marijuana, how can we justify not using it as medicine? Can it be regulated? Who can even regulate it?
Used in the right way, medicinal marijuana would undoubtedly prove to be useful for a variety of patients needing medication due to anything from the side effects of chemotherapy to the treatment of MS. But how do we do this?
Marijuana and the Endocannabinoid System
During the week of October 7 in my neurochemistry class, we explored and discussed the most commonly used illegal drug in Western societies, marijuana. Throughout the week, we discussed many different aspects of the drug, such as the endocannabinoid system, its process of binding within the body, the release and uptake, and any beneficial aspects that marijuana may have for a person. Personally, I found this article to be very interesting and informative because marijuana and endocannabinoids are two things that I know very little about, and I’m sure this is true for the majority of the general public. Even after reading the paper and discussing it for a week, there is a lot that I don’t completely understand, but I hope to convey the information as accurately as possible.
In order to understand the endocannabinoid system and how marijuana is interrelated, it is important to first understand the basics of marijuana. The genus species name of the marijuana plant is Cannabis sativa. For hundreds of years, it has been used for medical and recreational purposes, and is the most widely used drugs in various countries throughout the world. Cannabis sativa contains at least 400 chemical components, in which 60 of them belong to the cannabinoid class. Tetrahydrocannabinol (THC) is the main psychoactive component of cannabis, and is responsible for giving people the feeling of being “high.” Marijuana, as well as other cannabinoids may be therapeutically useful, but this is greatly hampered by their psychotropic effects and by their potential for abuse. Research is currently being carried out to find new approaches to harness the therapeutic properties of marijuana without causing unwanted effects.
Important to the function of endocannibinoids is their binding to G-protein coupled receptors (GPCRs) on the cell surface. GPCRs work by binding a G-protein, which activates the complex by producing GTP from GDP. This complex then goes on to activate the enzyme, adenylyl cyclase, which produces the second messenger, cyclic AMP. Lastly, cyclic AMP carries out many different functions in the cell. Endocannibinoids bind to two different types of GPCRs: the CB1 receptor and CB2 receptor. The CB1 receptor is present throughout the central nervous system and is highly expressed in the cortex, hippocampus, basal ganglia, and cerebellum. They have effects on memory, movement, and nociception. Unlike CB1, the CB2 receptor in primarily expressed in the immune cells and carries out important functions in the immune system.
After their biosynthesis, endocannabinoids are released to extracellular space and activate the receptors by membrane diffusion or by a transporter. Due to their lipophilic nature, endocannabinoids can diffuse through the plasma membrane and bind to the appropriate GPCR. In addition to the psychotropic effects that marijuana has after it binds to a receptor, marijuana can also have helpful therapeutic effects for a person. Marijuana can help treat an eye disorder called, glaucoma. During our discussions during the week, we talked a lot about other therapeutic effects that marijuana can have. One student in our class mentioned that his relative is prescribed medical marijuana to help ease chronic pain back pain. He said the marijuana has a significant impact on the reduction of his pain. We also watched a video in which a patient uses medical marijuana to reduce the symptoms of Parkinson’s disease. In the video, you could definitely observe the fact that the marijuana helped reduce the symptoms. As you can see, marijuana doesn’t only have negative effects, but it can also have helpful therapeutic effects.
http://www.youtube.com/watch?v=KdvprGD5TXU
Connection Between Diabetes and Alzheimer's Disease?
Over the past week in my neurochemistry class, we explored and discussed a very interesting new discovery in the pathogenesis of Alzheimer’s disease. It has been discovered that type 2 diabetes mellitus is a significant risk factor for Alzheimer’s disease. Insulin resistance and glucose metabolism of patients with diabetes mellitus are the two main implications for developing this neurodegenerative disease. Personally, I found the article that we read to be very interesting and was amazed by the fact that two unrelated diseases in terms of pathogenesis can actually be interrelated and have connections with one another. Even after reading the article and discussing the topic for a week, I still don’t quite understand everything, so I will stick to the basics when describing this topic to you.
In order to understand the connection between type 2 diabetes mellitus and Alzheimer’s disease, it is first important to know the characteristics of each disease. Alzheimer’s disease is a neurological disorder characterized by profound memory loss and dementia. The pathological hallmarks of Alzheimer’s disease include a few obscure scientific terms such as, amyloid plaques, neurofibrillary tangles, and amyloidal angiopathy. Loss of neurons and synapses in the central nervous system is also observed in patients with this disease. Types 2 diabetes mellitus is characterized by excessive amounts of glucose in the blood primarily because they are insulin resistant or are insulin deficient.
Like I mentioned earlier, type 2 diabetes mellitus is a significant risk factor for developing Alzheimer’s disease. It has been determined that insulin has important outcomes on brain functions in addition to numerous peripheral metabolic effects. There are two models that describe the connection between diabetes and Alzheimer’s disease. They include central insulin resistance and inflammation in the brain. Both of the models influence insulin sensitivity in the brain, which leads to B-amyloid accumulation and eventually to Alzheimer’s disease.
Insulin is primarily synthesized in the pancreas and has very important roles in metabolic homeostasis. There is evidence that insulin is also produced in the brain. It has important effects in the central nervous system, regulating key processes such as energy homeostasis, neuronal survival, as well as learning and memory. In patients with type 2 diabetes mellitus, the transport of insulin into the brain is reduced, which in turn decrease brain levels of insulin. Studies have linked the reduction of insulin in the brain with Alzheimer’s disease suggesting that the brain must be influenced by insulin levels and sensitivity. Another interesting aspect of the connection between diabetes and Alzheimer’s disease is the implication of glucose metabolism in Alzheimer’s disease. Utilization of glucose by the brain as a source of energy is important for many of the processes that the brain carries out. Abnormalities in the brain of Alzheimer’s patients are connected with alterations in brain metabolism. These alterations are often associated with impaired glucose utilization and energy metabolism, which are two features of type 2 diabetes mellitus.
I have never heard that type 2 diabetes mellitus is a significant risk factor for developing Alzheimer’s disease, so it was very interesting learning about the many factors that play a role in the connection between these two diseases. Learning about this connection has made me more aware and conscious of the decisions I make regarding how much and what types of food I consume.
Nuts and Bolts of the Akt/GSK3 Pathway
Over the past week in my neurochemistry class, we discussed and learned more about an important pathway in the brain. The pathway I am referring to is called the Akt/GSK3 pathway. In order to learn more about this pathway, we discussed the article, “Beyond cAMP: The Regulation of Akt and GSK3 by Dopamine Receptors.” Even after spending a week of learning about this topic, I still have many questions that have been unanswered. On the other hand, this past week has been very beneficial and has significantly advanced my understanding of this complex topic. The Akt/GSK3 pathway has implications in the actions of antipsychotic, psychostimulant, and antidepressant medications. It is also involved in schizophrenia, bipolar disorder, so it is important to understand the basics of this pathway.
The article begins by summarizing the mechanism of the Akt/GSK3 signaling cascade. Research has shown that dopamine may play a role in the regulation of Akt and GSK3 signaling. The D2R receptor is directly involved in this pathway and its activation stimulates the formation of an important signaling complex. This signaling complex is composed of three molecules: beta-arrestin 2, PP2A, and Akt. The formation of this complex results in increased inactivation of Akt. An important discovery by researchers is that lithium disrupts the formation of this complex and inhibits the activity of GSK3. Lithium is able to disrupt the complex by directly preventing the interaction of Akt and beta-arrestin 2. Inhibiting GSK3 is the mechanism of action that many antipsychotic medications utilize.
Here is a diagram of the Akt/GSK3 pathway, which will hopefully make the pathway a little clearer and easier to follow.
In addition to having implications in antipsychotic medications, the Akt/GSK3 signaling pathway plays a role in neurodegenerative diseases, such as Parkinson’s disease. Currently, it is unclear what the mechanism is behind the role that the Akt/GSK3 pathway has in Parkinson’s disease, but researchers have discovered two neurotoxins that play a role in this disease by studying model rats. Further research on the mechanism of Parkinson’s disease will hopefully lead to an effective way to prevent this disease.
Like I mentioned earlier, the Akt/GSK3 signaling pathways plays a role in the action of antipsychotics. Several antipsychotics have been shown to be able to activate Akt and inhibit GSK3. In my opinion, it is exciting that researchers are constantly discovering different ways to produce effective medications that are useful for various different diseases. The Akt pathway is only one pathway that is utilized in the production of medications. It will be important for researchers to continually produce medications, and it is exciting that researchers are working daily to produce new effective and efficient medications.
Over the past week, it has been very interesting to learn about this important signaling pathway in the brain and see how it can be utilized in the production of numerous medications. Discussing the article has made me aware of the fact that signaling pathways in the brain are very complex and can be difficult to completely understand.
The Concussed
When a concussion occurs, the first few hours are when the neurological damage really occurs, and the weeks after the injury are when the side effects start to be noticed. Neurons are forced to work overtime due to the rapid metabolism of glucose after a concussion. Hypometabolism occurs in the first few hours of the injury, and the recovery time of this hypometabolism is dependent on the degree of the concussion. This metabolism rate is not the only dependent on intensity of the concussion; the amount of damage the axonal cell membranes endure is also related to how bad the concussion is, and this axonal injury is connected to spatial learning and memory deficits. It makes sense that with worse injuries, the patient’s memory is at more risk.
The effects repeat concussions have on the brain is very influential to the person’s memory, learning ability, etc., which is why it is extremely important to make sure that a person is completely recovered before they are put back into a situation where they could potentially get another concussion. Thankfully there have been regulations limiting the amount of concussions a person can have before they can no longer play a sport. However, this poses the problem that some concussions go unreported. For many athletes playing in a game is more important at the time than their long term health.
Concussions have been a topic of debate that has essentially changed the way contact sports are played. Although many of the changes are beneficial and were necessary, I do believe that the game has changed so drastically that we may be doing more damage than good. It’s not a secret that with new padding and equipment players are more likely to use more force when coming into contact with another player. Comparing how hockey is played in 2013 and how it was played 60 years ago, the only obvious commonality they have is that it is played on ice. I’m sure the reported amount of concussions in the 1950’s would not be accurate, and neither would the amount of reported concussions in 2013, but I believe for completely different reasons. An athlete can only report so many concussions before they are out of the game, whereas in 1950 it may not have been sociably acceptable to have a concussion, both cases leading to an inaccurate number of reported concussions and an athlete that is at risk for permanent long term memory defects. As we learn more about the long lasting effects of concussions, sports are bound to change even more, which may be met with resistance, but hopefully it will help athletes in the long run.
I think you were dropped on your head as a child.
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.