What comes to your mind when you think of Parkinson’s Disease? Shaking, tremors, spasms and Michael J. Fox were probably at the top of your list right? There is a lot more to Parkinson’s Disease (PD) than people think as well as many new research discoveries that could lead to effective treatments for this disease. People may know little to nothing about how PD works, so let me take you through a brief description of what is going on in a persons brain and body when they have this disease.
Parkinson’s Disease is a degenerative dissorder of the central nervous system. It usually affects older individuals (over the age of 50) and cannot, as of yet, be cured. PD causes many motor dysfunctions as it is a result of the death of dopamine-generating cells in the substantia nigra within the midbrain. This loss of cells causes many visible symptoms in the early stages of this disease such as bradykinesia, resting tremors, rigidity, shaking, slownesss of movement, diffiulty walking, and overall uncontrollable movements. While this dieseae advances, it still shows these visible symptoms but also can start causeing autonomic dysfunction and affecting the persons cognition. Depression is often one of the most common psychiatric symptoms and dementia usually occurs in the later stages of this dissorder. There is a protein called alpha-synuclin, that usually helps in mediating cell death, that gets disrupted and leads to Lewy body formations in the brain.When Lewy bodies form, this is what casues the loss of dopaminergic neurons, which ultimately causes a loss of dopamine release and the symptoms of PD.
There has been tramendous research done to try and find out why this disease occurs and what could be targetted for treatment. In the article we read this week for neurochemistry called “Targeting dysregulation of brain iron homeostatsis in Parkinson’s Disease by iron chelators”, the authors focused on the role that iron plays in people who have PD as well as how understanding brain iron accumulation could lead to a very effective treatment for this disease. Many scientists have discovered that the excess iron accumulation within the brain may be causing a build up of the alpha-synuclein (this is not good!). Because of this researchers are trying to find a way to stop the large accumulation of iron in our brains that happens as we age. In the article the authors discussed something that is still being researched but could slow and or stop the iron accumulation all together. It is something called an iron chelator which is essentially something that binds to iron in the brain and removes it so it does not build up. Researchers think this is a large step to helping treat the high levels of iron found in PD patients and ultimately improving the lives of these individuals living with this disease. These chelator’s are not fully understood yet, but they are something that could help slow the progression of Parkinson’s disease.
I do not fully understand everything that is going on inside a person’s brain when they have PD, but I do know that it is something we all should be aware of especially while looking at possible treatments for these neurodegenerative diseases, not only PD but also Alzheimer’s disease, and Huntington’s disease. If we are all made aware of what we can do individually to live healthier lives and be educated on the research of these diseases, then maybe one day there will be less people diagnosed with PD (or other degenerative diseases) and more effective treatments for those suffering from them. In class we discussed how drinking green tea may lead to regulating iron levels in the brain. Is it super scientific and 100% effective? Absolutely not. But it could be something we could do in our everyday lives to help lower the levels of iron accumulation in the brain.
What Can't Lithium do?
There are many different pharmaceuticals that have different effects within the body. These pharmaceuticals are many different elements. The simple pharmaceutical though is the ion Lithium. Lithium has many different effects on the brain. It covers a wide variety of disease and it has many different uses. The main function of Lithium is that it is neuroprotective. This means that it lessens the oxidative stress and causes less cell apoptosis to occur. There are multiple theories that try to explain the pathway that Lithium has in the brain. It is also involved in many different pathways with in the brain. One of the pathways that Lithium blocks is the IP3 pathway. In this path way Lithium blocks IP3, which is leads to the prevention of apoptosis. This is because IP3 signaling is linked to p25 and Cdk5. Both of these are factors in the cell that leads to cell death. Another function of Lithium is to block the NMDA-R receptor. This receptor triggers a signaling cascade that will eventually lead to cell death. Another function of Lithium is to activate cyclic AMP. Cyclic AMP will then activate PKA, which will block the GSK-3 pathway. Lithium can also directly block GSK-3. By inhibiting GSK-3, lithium is able to promote CREB, which is a transcription factor. This will promote transcription activity of anti-apoptosis proteins. This will lead to more cells surviving within the brain.
With all the pathways that Lithium is involved in, it can be used to treat many different neurological diseases. One of the diseases that it is used the most to treat is bipolar disorder. To treat this disorder, Lithium acts on the GSK-3 pathway. Lithium only seems to treat the manic stage of bipolar disorder. Another neurological disorder that can be treated with Lithium is strokes. Lithium can be used as both a preventive and post stroke treatment. If Lithium is administer after a stroke has occurred it has to be within 12 hours with daily injects for two weeks after. This is because the effects will not be as beneficial after this time period. A third neurological disorder that can be treated by the use of Lithium is depression. This seems weird in bi polar disorder lithium is given to treat the manic stages. Lithium is given for depression, but it is a last case scenario. It is only used if there are not any other drugs are able to treat depression. With depression treated by Lithium, it is thought that Lithium acts on the NMDA-R receptors.
One of the most interesting areas of research with Lithium is the possible treatment of fetal alcohol syndrome. Lithium decreases the amount of oxidative stress that is placed on the brain when alcohol, specifically ethanol, is in someone’s system. So far this has only been tested with mice in laboratories. One set of mice were able to birth a set of offspring without any alcohol. Another set of mice were given alcohol when they were pregnant. The offspring of these two sets of mice were then measured to see the cognitive differences. Once this was complete, the researchers then gave alcohol to the mice and lithium. The mice then birthed their offspring and the cognitive abilities were measured. In the end, the offspring that were given lithium when alcohol was in the system performed better than the ones that were not given Lithium. This showed that in mice, Lithium was able to decrease the effects of fetal alcohol syndrome. The problem with this though is that this may give mothers an excuse to drink while they are pregnant and what would happen if they forgot to take the Lithium pill?
Type 3 Diabetes: Alzheimer's Disease
There are many health concerns that are related to diabetes. One of the new outcomes of diabetes is that there is a possibility of a having a higher chance of getting Alzheimer’s disease. The reason for this is the large role that insulin plays in the brain. In type 1 diabetes, formerly known as juvenile diabetes or insulin dependent diabetes, a person’s pancreas is not able to produce insulin or they do not produce enough insulin. Insulin is important throughout the body because it allows glucose to be broken down and taken into the cell. The other form diabetes is type 2 diabetes and it occurs when the body becomes resistant to the effects of insulin or doesn’t make enough insulin. This seems like it would affect the body of a person the most, but the brain is also affected by the lack of insulin or resistance to insulin. There are three main functions of insulin in the brain. The first of these is that insulin down regulates tau phosphorylation. This then causes lees oxidative stress to occur in the brain. This leads to less cell apoptosis and less synapses being destroyed. The second function that insulin has in the brain is to increase the CSF norepinephrine. This helps control the cognitive function in the brain and it also increases the mental control of the brain. This allows for individuals to be able to have better memory with more insulin in the brain. Third role that insulin has in the brain is for insulin to increase the glucose metabolism in the brain. When this occurs, it has been shown that the person’s cognitive ability has increased.
One of the next big questions that can be asked from this is how big of role does our diets play in this process? Many people eat unhealthy and give little concern with it. Would someone’s perception change if they knew that it could affect their memory in the future? The answer would seem to be yes, but it seems that many people do not feel that way. This is because many people are making unhealthy choices with knowing the preexisting consequences. If people knew of another reason to eat healthy such as this, they may want eat healthy. Another concern that comes with diet is the idea that maybe should be taking insulin as a preventive treatment. This would seem to be a good idea but this would also be very difficult. It may also give people an excuse to eat food that is unhealthy. This would cause many other health concerns. Another problem with eating healthy is the idea that healthy foods are hard to access or they are too expensive. This is a concern to people that tend to eat unhealthy. If people are going to try to eat healthy, this would have to change in order for them to be able to eat healthy.
Marijuana the Miracle Drug
One thing that is seemed to be looked down upon in society is the use of medical marijuana. But how can something that seems to have so many positive side effects be looked upon as something bad. This may because marijuana is known as a “gateway drug” or that is often associated to people that have a lack of motivation or have poor social standing. Another reason for this is that a person may not know the many positive outcomes with using medical marijuana. The list of the diseases and issues that it treats is longer than many other modern medicines that any scientist has made. These are all possible uses for medical marijuana:
- Nausea and Vomiting
- Anorexia and Cachexia
- Spasticity
- Movement Disorders
- Pain
- Glaucoma
- Epilepsy
- Asthma
- Dependency and Withdrawal
- Psychiatric Symptoms
- Autoimmune Diseases and Inflammation
These are only some of the medical issues that are treated with medical marijuana. One advantage that is overlooked with medical marijuana is the fact that is it is natural. This means that marijuana, for the most part, is a natural substance that is no chemically synthesized in the lab with many different chemicals. Many of the pharmaceuticals that are used today or that are made by big businesses are made by the combination of many different chemicals that are added together. Medical marijuana is grown by licensed and heavily monitored farmer. Medical marijuana is grown in the soil and is a plant. This seems to be safer than the man-made pharmaceuticals.
But how does all these positive affects seem to occur within the body? This is because some of the active chemicals within the medical marijuana are very similar to those that are in the human body. The main chemical components that make up marijuana are cannabinoids. There are 60 different cannabinoids that can be found within the marijuana plant. The high feeling is that is associated with marijuana is caused by the chemical Tetrahydrocannabinol (THC). This is considered a cannabinoid. These 60 chemicals that are in marijuana are able to interact with the endocannabinoid system that is within every human’s brain. The cannabinoids that are in marijuana bind to the G-protein coupled receptors that are meant for the human endocannabinoids. This allows for the signaling cascades that are associated with endocannabinoids to occur. This is because endocannabinoids allow for the feeling of pleasure and reward to occur. By using medical marijuana, people are able to feel that pleasure and don’t have to feel the pain that is associated with their disease or hardship.
One of the problems with medical marijuana is that is not much that is reported about the negative side effects of the drugs. It almost seems that there is too much that is good about the drug and not enough bad things. This is because so many modern drugs tend to have many side effects that are associated with them and the that medical marijuana hardly has any is kind of alarming. But if it is helping this much without any side effects, maybe it should be legalized more and should be prescribed more in medical institutions.
Akt/GSK, How Important is it?
There are many different issues that are covered on this topic that are important. The pathway that is the main concern for this article is the AKT/GSK pathway. This is a lesser known pathway, but can also cause many issues if it is not correctly dealt with. This pathway is linked to many other neurotransmitter pathways in the brain so one fault in this pathway can cause issues somewhere else. Some of the diseases that can occur of this pathway are depression, schizophrenia, Parkinson’s disease, and Alzheimer’s disease.
One of the first diseases that is mentioned in this article is depression. This is associated with low levels of GSK. This low level of GSK is typically caused by low amounts of dopamine within someone’s system. This makes sense because dopamine is usually associated with the reward system of the individual. If dopamine is low, a person is not being stimulated enough. This causes less dopamine to be released, affecting many pathways within that individual’s brain. The GSK pathway is one of those affected by lowering the level of GSK below normal.
Another disease that can be associated with the AKT/GSK pathway is schizophrenia. The issue that is dealt with in this paper is the treatment of schizophrenia by using this pathway. The researchers suggest that this could be a possible target for future pharmaceuticals. These drugs would target the AKT1 molecule. This is because people with schizophrenia typically have lower amounts of Akt1 within their system. Another target molecule fir this system would be GSK. With having less Akt1 molecules there would be more GSK molecules that are not phosphorylated. This means that the complex of GSK would be in its active state. The pharmaceuticals would target this molecule and try to inactivate it so it cannot work anymore.
A third disease that is discussed about in this paper is Parkinson’s disease. Parkinson’s disease may be caused by a lower amount of dopamine in the brain. Many of the modern pharmaceuticals that treat this disease try to increase the amount of dopamine within the brain. When studying the effects of Parkinson’s disease researchers found out that the amount of dopamine caused there to be a decreased amount of AKT and GSK. This is what causes researchers to think that the AKT/GSK pathway may be involved with the onset of Parkinson’s disease.
Overall it can be seen that Dopamine and this pathway is a very important part of everyday functioning. This pathway can also cause much harm within the brain if it has become unbalanced. This is when the pathway needs to be monitored. From this pathway, there can be treatments for the above listed diseases. This pathway can also help diagnose potential diseases that are still hard to diagnose. Dopamine is a very important neurotransmitter in the, but everything that is good there is some harm that can go along with it.
What's the real problem?
There are many factors that seem to play into the development of autism including genetics, the mother’s diet, the child’s diet, as well as the physical health and age of the father. There is a lot left to learn about autism, and with the amount of children being diagnosed with autism, research better be done in an effective manner. However, this amount of children diagnosed with autism could be the result of various onsets. A major player in this is that the autism spectrum has been broadened. There is a whole category of autism designated by “unspecified.” For me, it is hard to understand how this is considered autism in the first place. If a child has something that is not categorized as autism, or something that is directly on the autism spectrum, why is it considered autism? I am starting to think that this disease is becoming a scapegoat for many children illnesses. This, in turn, can be harmful to the child who won’t get the correct kind of help he/she needs.
A reason for this spike of children being diagnosed with autism that I cannot seem to get away from is just how much our lifestyle has changed. There are pesticides and GMOs in almost everything, I wonder if it is directly correlated to this disease. Not only the alteration of food genes, but also the way we consume food as a society. It is almost impossible to get food that has come from the same state we live in, especially in the Midwest in the winter. The growing season is not long, so we have fixed this problem not by building better storage devices, but rather changing the food we are eating. I don’t understand how this can be safe for future generations who will know anything but genetically modified food. Of course not everything about altered food genetics are bad, but it is interesting that as soon as we start to change what we eat, especially mothers who are pregnant, we see changes in the generation that follows.
Children who are born with autism are obviously directly influenced by his/her mother, which is why the diet for pregnant women is so strict. If a child does not have enough good fatty acids in his/her brain, there is a much higher change that that child will have inflammation in his/her brain and the brain will not be able to develop in a way that is considered normal. This is also true after birth. A child on the autism spectrum has to undergo a lot of therapy, and surprisingly a lot of dietary restrictions. Many of these restrictions come from food intolerances, but a diet with lots of good fats (poly-unsaturated fatty acids) are seen as helpful for a child with brain development issues. Although it is still being study, they may be able to help prevent, or even in some cases reverse, autism and autism symptoms.
There is a lot that needs to be done in order to help people who have autism, and understand how this disease works. I also believe that it is important to understand why there is such a drastic increase autistic children. This is yet again another reason to take a look at how our society, as a whole, has changed and possibly do away with many of the “helpful” changes we thought would do no harm to us and the future generations.
Oops, which kind of Iron?
Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, affecting movement, thinking, and behavior. Mostly affecting those over the age of 50, it believed that as many as one million Americans live with PD. There is no cure for this disease, and scientists are still trying to understand what is really going on. The article our class focused on this week was called “Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators.” The main focus of this article was on the role that iron plays in those with PD. It has been seen that those who suffer with PD have elevated levels of iron. We’ll have to look into a little bit of science to see why this matters.
There is a protein in our bodies called alpha-synuclein. Aggregation of this protein causes the formation of something called Lewy bodies. When Lewy bodies form, this causes a loss of dopaminergic neurons, and therefore causing a loss of dopamine released. Due to this, these Lewy bodies can cause many complicated, negative effects within the brains of those affected with PD. So how does iron fit into this picture? Scientists have seen than excess iron can may cause a buildup of alpa-synuclein. Due to this, many scientists are attempting to understand how to stop this excess iron from building up. The main way under investigation includes the use of something called an iron chelator. On the most basic terms, an iron chelator binds to iron and removes it, helping regulate these high levels of iron found in PD patients. Iron chelators, though not completely understood yet, have shown promise in the treatment of Parkinson’s disease.
If you’re anything like me, you don’t care as much about the scientific details, but how this pertains to our lives. Yes, understanding the details is important, but what’s more important is what we can take away from those details and how we may change our life choices to lead a happier and healthier life. As we have seen, iron accumulation is not something that we want, but unfortunately it is not something that we can completely avoid. Though reasons are still not clear, iron accumulation occurs as a function of age. Besides use of iron chelators, there has been evidence of helpful natural solutions. Green tea has been shown to contain molecules that may be helpful in regulating iron levels. Though green tea will most likely not be the cure for Parkinson’s disease, it may be helpful! Maybe even a cup or two here and there couldn’t hurt! Seeing this, reminds us once again the overall importance of eating and drinking healthy to put beneficial and not harmful chemicals into our bodies.
Hope for Autism
This week, our neurochemistry class moved away from typical discussion of neurodegenerative diseases to focus on autism, a neurodevelopmental disease. The prevalence of autism has increased 600% over the last two decades. Autism is one of three autism spectrum disorders (the other two are Asperger syndrome and pervasive developmental disorder, not otherwise specified (PDD-NOS)). Children usually first start showing signs of social/emotional impairment, repetitive behavior, limited interests, and atypical eating patterns before the age of two. Unfortunately little is known about the cause of the disease, which limits the treatment and therapy options available. Scientists do believe that the increase of autism can be attributed to a combination of both genetics and the environment. Overall, autism is thought to result from disorganized connections between neurons in the brain. Several hypotheses attempt to explain the cause of the disorganization in the brain.
One of the hypotheses currently suggested is that decreased acetylcholine signaling is responsible for the development of autism. It has been observed that autistic patients have fewer acetylcholine receptors in the brain. These receptors are responsible for relaying signals about pain and producing anti-inflammatory signals. More research needs to be done to further clarify how acetylcholine contributes to the development of autism. Most of the other hypotheses about the pathogenesis of autism involve the mother and the influence of prenatal environment. Some studies suggest that maternal infection while the fetus is in utero may increase the likelihood of developing autism. Other studies support the belief that increased prenatal stress will increase the likelihood of developing autism. The hypothesis discussed in the article “Autism as a disorder of deficiency of brain-derived neurotropic factor and altered metabolism of polyunsaturated fatty acids” is that maternal nutrition, specifically polyunsaturated fatty acids (PUFAs), plays a significant role in the development of autism. PUFAs control energy use in the brain and the amount of acetylcholine that is released. Memory, learning, neurite growth, and synapse formation are all promoted by increases in PUFAs. PUFAs also prevent cell death and inflammation. Additionally, PUFAs are known to increase brain-derived neurotrophic levels, which are important for brain development, learning and memory. Researchers believe that PUFAs and BDNF are involved in the development of autism because levels of PUFAs and BDNF are significantly decreased in autistic patients compared to healthy controls. PUFAs are also decreased in patients with conditions such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and dyslexia. It is believed that supplementing the mother’s and the child’s diet with polyunsaturated fatty acids could improve autistic symptoms and possibly reduce the likelihood of developing autism.
Parents of children with autism know there are very few treatment options available currently. Most autistic children participate in early, intensive therapy (at least 25-40 hours per week) in order to improve language skills, imitation, play, and motor skills. 3-25% of children with autism will no longer be on the autism spectrum after early behavioral therapy intervention. However, intervention is only effective in reversing or treating autism in some cases. Further research into the effects PUFAs and BDNF administration could provide a new avenue for treatment to prevent or reverse the development of autism in a greater percentage of children.
Insulin, Diabetes and a Whole Lot of Alzheimer's
According to the American Diabetes Association, in the United States, about 8.3% of the total population has some form of diabetes. That means about 25.8 million Americans are diagnosed with this metabolic disorder. As I have gotten older, the number of Americans in the U.S. has been increasing at an alarming rate. In 1991 about 6.9 million Americans were diagnosed diabetics. That number has nearly quadrupled in size from 1991 to now. This alone is very alarming, but if you also take into account the cost of controlling diabetes, the health complications, and now the increasing rate of Alzheimer’s disease (AD), it appears that this epidemic must be addressed more in our society.
There are three different types of diabetes: type I, type II, and gestational. The most prevalent is type II diabetes, and occurs when the body is unable to produce enough insulin, or the cells in the body begin to resist the insulin the body produces.
A lot of research has been looking at any correlation between type II diabetes and Alzheimer’s disease, and the research has been proving to show that there may indeed be a relationship. Alzheimer’s disease is a neurodegenerative disease where things called amyloid beta plaques and tau tangles build up in the brain, causing neurons to die and leading to impaired memory and cognitive dysfunction. Due to the decrease in insulin within the brain, or the increase in insulin resistance, insulin is unable to properly carry out its functions. This can lead to Tau hyperphosphorylation and neurofibrillary tangles along with amyloid beta plaque formation, all of which are the cause of AD.
Above is a figure showing how both type 1 and type II diabetes can lead to Alzheimer’s disease. Note how not just type II can be a risk to AD.
What is so unfortunate about this relationship between AD and Type II diabetes is that with the increasing numbers of diabetes in the United States, there will also be an enormous increase in AD, especially in the future. The chances of someone getting AD increases as we get older, and if one also has type II diabetes, the chances of having AD becomes a scary number. So then, the next question is how do we help prevent AD, or even diabetes to occur? Insulin may be the answer. Insulin injections are great regulators for people with diabetes, and are already being used as treatment. However, this only stops the symptoms, and is not a cure.
So what are the true keys to helping battle diabetes, preventing diabetes, and lowering the chances of getting AD? They are exercise, a healthy diet, and education. We’ve been hearing it since elementary school, and many of us still don’t recognize these three important things. Exercise not only helps with blood sugar, but also is healthy for our whole body. A healthy diet seems like a difficult option in today’s society, and I agree, but it’s definitely doable. Finally, being educated on how to keep your body healthy and learning more about what we eat can go a long way in helping how we shop at the grocery store. It seems like a hard task that may empty out the pocket, and I won’t deny that that may be a possibility. But one must weigh the risks, and I believe that living a healthy lifestyle will definitely be worth every penny.
Marijuana???
Should smoking marijuana be legal? Should using marijuana for medicinal purposes be legal? These are some hard-hitting questions that, in today’s society, are difficult to ignore. Some of the topics in our science classes can seem a little dry and boring to the general public, but it’s hard not to have an opinion on this week’s subject.
The article we looked at this week, “Endogenous cannabinoids revisited: A biochemistry perspective” looked into the chemistry of what is really happening when marijuana enters our system. Specifically, what happens in our brain and what implications this may have for medicinal purposes.
Marijuana has long history of being seen as a terrible and useless drug that makes people lazy and hungry. Not many people have a clue, (or want to admit they have a clue) that marijuana can be used for medicinal purposes. Could smoking weed really help people? In our society today, it seems like a crazy thought. But it’s true, and there is science to back it up!
A little science for ya:
The active ingredient in marijuana is tetrahydrocannabinol or THC. Humans produce endocannabinoids which act similar to THC, anandamide (AEA) and 2-arachidonoyl glyceride (2-AG). AEA and 2-AG bind to cannabinoid receptors, and THC mimics these actions and also binds to cannabinoid receptors. By binding to these receptors, THC causes adverse effects on the mind and body.
Many people smoke marijuana recreationally due to it’s psychological and physiological effects, making users feel relaxed and mellowed, bringing a sense of joy and entertainment to many. Of course it is important to note that marijuana can also have negative effects, such as problems with memory and learning, distorted perception, difficulty with thinking and problem solving, and loss of coordination. In spite of these side effects, scientists are looking into potential benefits to using marijuana for medicinal uses. Marijuana has been known to suppress nausea, relieve eye pressure, decrease muscle spasms, stimulate appetite, stop convulsions and eliminate menstrual pain. Medical marijuana has been seen to be helpful in many disorders such as alcohol abuse, asthma, bipolar disorder, depression, epilepsy, Huntington’s disease, leukemia, sleep apnea, anorexia nervosa, etc. The list really goes on and on. The fact that marijuana can be beneficial is really undeniable. The situation becomes difficult simply because of so many users that use for recreational purposes, and also the stigma behind the drug. Many patients who are in need of help, put off trying medical marijuana simply because of how it is seen in the public eye. If medical marijuana were to be made legal it would take time for the public view to change.
As of right now there is and will continue to be much controversy over legalizing marijuana. Due to its past and stigma, many people will continue to stand against the legalization of marijuana. There are many reasons why I believe that legalizing marijuana would not be such a bad thing, and this article only enforced those thoughts. The science behind it is fairly clear; there are not many, if no major or long term negative effects. In comparison to substances such as tobacco and alcohol, this simply confuses me. According to the World Health Organization, alcohol kills 2.5 million people per year. The information for cannabis provided by the World Health Organization does not even mention death. This statistic alone, speaks volumes. I am not saying that all marijuana should be legal, but I believe that both recreational and medical purposes for marijuana should continue to be looked at closely.
http://science.howstuffworks.com/marijuana3.htm
http://www.who.int/substance_abuse/facts/alcohol/en/