The brain is a mysterious part of our bodies, and we have yet to explore all its depths. It is made up of complex networks of billions of neurons, which control all the mechanisms and functions within the body. Because we do not completely understand the brain’s entirety, it makes it hard to learn about neurological diseases and even harder to diagnosis them. Recently, these disorders have become major points of focus for researchers and they have been able to shed some light on what is going on in the brain. These new understandings have allowed for treatments and therapeutic options to be discovered for many neurological diseases. Bipolar Disorder is one disease that has become an interest to many and in the last decade researchers have been trying to explain what is going wrong in people with the disorder. The disease is characterized with manic and depressive mental states. However, a person with Bipolar Disorder can have varying amounts of these states and activities during them. During the manic phase, the individual can experience high self-esteem, risk-taking behavior, and excessive energy, making sleep negligible. On the contrary, the depressive state consists of changes in appetite, sleep, interests, and suicidal thoughts and/or actions. These states are in constant fluctuation, making it hard for a person to live a normal life. Individuals are normally diagnosed in their early twenties, but can have symptoms years before an actual diagnosis.
For many years, not much was known about Bipolar Disorder or the medications that help to treat it. Recent studies have suggested that it is a complex disease, with many contributing factors. These factors include over activation of glutamate receptors, also known as excitotoxicity, oxidative stress, and inflammation of the brain. Many of these symptoms are also common in other neurological disorders such as Parkinson’s disease, Alzheimer’s disease, and traumatic brain injury. In Bipolar Disorder, when the brain becomes inflamed it activates a cytokine pathway, which is a cell signaling molecule usually involved in the immune response. In Bipolar Disorder it is not exactly known what activates these pathways. However, these pathways have been shown to increase the number of oxidative species in the brain; we normally refer to these as free radicals. These radicals further damage the cell’s ability to effectively perform, eventually leading to cell death. Not much is known about why the brain in these victims becomes inflamed, but this inflammation is also seen in concussions, and may be the result of an injury to the brain causing these effects.
With many other disorders having similar characteristics, it makes it hard to diagnosis Bipolar Disorder. The argument has become whether or not these diseases are over or under diagnosed. Because so little is known about disorders affecting the brain, many times people do not know what is going wrong until years after the initial symptoms first started. At that point, much of the damage that has occurred is irreversible. Many factors can contribute to delayed diagnosis, such as the age at which people are diagnosed, ruling out other diseases, and substance abuse. For the most part, the age at which people are diagnosed is a time when many things are going on in these individuals’ lives. They are most likely graduating high school, going to college, getting jobs, and some are starting families. The stress of these life events can make it seem like nothing is wrong and that the manic and depressive episodes are simply the person trying to deal with the fast pace of life. Also, years before diagnoses, many individuals are in there teens, trying to find their individuality, going through puberty, and so forth. These episodes can then seem like the average rebellious teenager and it is not until years later, after a diagnosis, that these people begin to see what was influencing their behaviors years ago. People diagnosed with Bipolar Disorder also many times abuse drugs and/or alcohol. This can make it hard for anyone around them, as well as themselves, to be able to understand what is going on with their mental state. They are already not thinking clearly and have thrown in another factor, such as these substances, making everything much more complex. All of these factors go on to further complicate the already complex neurological disease.
After looking at all these factors, we still have much more to learn about the brain. The brain is so intricate, making problems within the brain just as complicated. Until we can better understand the depths of the brain, there is no saying how well we are diagnosing and treating these disorders. Once we are able to reach these depths in understanding, there is no telling the numerous amount of treatments, maybe even cures, that could be possible for neurological diseases like Bipolar Disorder.
References:
http://www.sciencedirect.com/science/article/pii/S0149763410001545#sthash.ATLQszpz.dpuf
Understanding the Highs and Lows of Bipolar Disorder
Bipolar disorder (BD) is a mental disorder known for its manic and depressive episodes. Unlike our previous topics, it is not neurodegenerative, but it is neuroprogressive. When I think about BD, I think of massive mood swings from the highest of highs and the lowest of lows. I think of chemicals imbalances in the areas of the brain that control mood. I don’t think of structural changes occurring in the brain that mark this as a neurological disorder. Even more than that, I don’t picture a brain that shares dysfunctional pathways with all of our other neurodegenerative disorders such as inflammation, excitotoxity, and oxidative stress. Bipolar disorder can be extremely hard to diagnose even with the new DSMV guidelines. The median age for BD is 25, a time when people are finishing school or entering the job force – in general, a very high stress times. It is not hard to imagine stress causing individuals to enter into a depressive or manic state depending on their coping mechanisms. It may take years to accurately diagnose. Especially in teenagers, who are commonly misdiagnosed with other psychological disorders such as ADD/ADHD and depression.
The neuroprogressive aspect of the BD makes it vital to try to accurately diagnose the disorder in the earliest stages. Brains with the disorder exhibit a loss in grey matter in the anterior limbic region responsible for executive control and emotional reasoning. However, the highest amount of grey matter loss occurs in the anterior cingulate cortex (ACC), which controls emotional responses and other cognitive functions. An individual with BD has the world working against them in manner ways. First of all, there needs to be a special combination of genetic factors, stressors, and aggravating factors, such a substance abuse, which illicit the disorder. The sum of all these factors manifests in manic and depressive episodes characteristic of the disease. As the time between episodes decreases, the severity of each one increases while the responsiveness to therapies decreases. Ultimately, BD leads to issues with cognition and mood modulation. Inflammation, oxidative stress and neurotrophic factors were focused on in this week’s paper. What makes certain brain mechanisms go awry? The paper suggests that is a lack of compensatory mechanisms within a BD patient.
There is no one drug therapy for BD, so patients end up taking a cocktail of medications that target both the mania and depression. One treatment seems to target many of the pathways suggested in the paper that contribute to BD pathology. Lithium has shown to decrease reactive oxidative species (ROS), increase BDNF – a protein which functions in cell growth, differentiation, survival – and inhibits proteins involved in the apoptotic pathway such as GSKα and caspase. In addition, lithium treatments increase mitochondrial expression of complex I, decreasing mitochondrial dysfunction and contribution to oxidative stress, and restores cytokine levels therefore decreasing inflammation. Aspirin is also used to decrease inflammation and ROS, and acts as an antidepressant.
As this week’s paper shows, there is a lot more happening in the brain of a patient with BD that what we see. Bipolar leads to increased mood and cognitive impairment because of the snowball effect of increased episodes in areas of the brain involved in mood regulation and higher order thinking. Treatments need to target the specific pathways that run awry. It is usually hard to target one pathway or one area of the brain for treatment. Remarkably, lithium seems to target a combination of pathways. As a society, we have a stigma around psychological disorders which puts anyone with one in a negative light. This stems from an ignorance of what is happening to people with such disorders. Bipolar disorder, as discussed, has so much more happening in the brain than chemical imbalances. I hope that people may do more research on BD and other psychological disorders so we can show more empathy and less judgment towards those with diagnoses of depression or BD.
We Are All Doomed
The pessimistic conclusion I have come to after about 2 months of studying various neurological diseases is that we are all doomed.
OK, not really… but sort of…
There are so many things that can go wrong in the brain that it seems something will go wrong in everyone’s brain… eventually.
The topic of the week in our neurochemistry class was bipolar disorder, BD (also called manic depressive disorder). BD is a neurological disease that affects about 5.7 adult Americans and has an average onset age of 25 (http://www.dbsalliance.org/site/PageServer?pagename=education_statistics_bipolar_disorder). BD is a neuroprogressive disease and thus worsens with age, but unlike some other neuroprogressive diseases like Alzheimer’s and Parkinson’s, aging is not a huge risk factor. So what makes BD different from other neurological diseases? That was the question we tried to explore.
Like other diseases we have discussed, BD has many, many contributing factors….
-Excessive dopamine neurotransmission contributes to the manic side of BD by way of increasing oxidative stress in the neurons.
-Similarly, increased glutamate levels are involved with BD by way of increasing excitotoxicity in the cells which causes a damaging calcium influx.
-Inflammation around the neurons may contribute to the depressive side of BD as it is usually associated with depression.
-Oxidative energy generation is involved in BD; increased in mania and decreased in depression.
-Oxidative stress in the mitochondria of the neurons leads to mitochondrial dysfunction and can create free radicals that damage the cells.
BD can be treated with medications including anti-seizure medications and lithium.
So what makes BD distinct from other neurological diseases? Many of the listed factors in the diseases are almost exact repeats of the things that go wrong with Alzheimer’s and Parkinson’s and ALS. The article we discussed does not really give a clear answer about the distinguishing characteristics of BD. It could be that it mainly depends on the types of neurons and locations of such neurons that are affected. It could also depend on when the neurons are damaged. Since BD has an earlier onset age and starts usually during development of the brain and AD and PD start much later in life, this factor could distinguish the diseases.
Regardless of the exact distinguishing factors, BD in severe cases is a debilitating disease that has similar characteristics to other neuroprogressive diseases. With every passing week, I am convinced that the brain is a delicate organ requiring the utmost balance in all of its processes, and with enough time… it is likely we will all get a neurological disease…. Let’s hope that is just me being pessimistic.
Article Reference: http://www.sciencedirect.com/science/article/pii/S0149763410001545
A Look into Bipolar
Mental illnesses have been more of a focus in medicine in the last decade because of the increased number of diagnosis. Bipolar otherwise known as manic-depressive disorder is one of the mental illnesses that have been a part of this. The average onset age is twenty years old. There have been instances juvenile bipolar too. Research is beginning to look at the effect of bipolar on children.
Bipolar is a disorder characterized by a manic and depressive state. Manic stage symptoms include higher self-esteem, little need for sleep, constant talking, racing thoughts, easily distracted, psychomotor agitation, and pursuit of pleasure with a high danger risk. Some of the depressive state symptoms are lack of interest, changes in appetite, changes in sleep habits, lack of energy, feelings of self-doubt, cognitive difficulties, and suicidal thoughts or actions.
It is a multifactorial disorder that includes inflammation, dopamine excitotoxicity, glutamate excitotoxicity, mitochondrial dysfunction, and oxidative stress. When the brain becomes inflamed, a cytokine pathway is initiated. These cytokines activate certain receptors, which increase the number of reactive oxidative species (ROS). These ROS are toxic to the brain and can cause dysfunction. Glutamate excitotxoicty causes a similar problem that leads to ROS being released. An increase in dopamine causes the manic state. This also leads to oxidative stress from ROS. These are just a few of the possible routes that can cause bipolar.
The most popular drug to treat the symptoms of bipolar is lithium. It reduces the oxidative stress caused by the pathways discussed above. It is a favorite because it can treat the manic and depressive symptoms. Patients with bipolar can be given valproate too, which also reduces oxidative stress. Many scientists are researching the mechanism of the drugs, since we don’t know the exact cause of bipolar.
I have a personal connection to bipolar disorder. One of my relatives has it. She had to drop out of school because she couldn’t handle it on her own. I’ve witnessed both parts of her illness. During the manic stage, she becomes very active. She will deep clean her house or go on biking and hiking trips. The depressive state is the worst. She sleeps at weird hours of the day. She becomes very quiet and stays indoors all day. It’s like she loses hope. It’s very difficult to watch someone you love suffer. Mental illness research needs to continue and expand because it affects so many people.
Sources:
https://moodle.cord.edu/pluginfile.php/390935/mod_resource/content/2/bipolar.pdf
http://neurochemistry2014.pbworks.com/w/page/88342886/Pathways%20underlying%20neuroprogression%20in%20bipolar%20disorders%20and%20neurotrophic%20factors
http://www.medscape.org/viewarticle/560302
Maybe We All Have a Mental Disorder
Bipolar disorder (BD) is a mental disease characterized by swings from a manic state to a depressed state. Although each individual is affected in a unique way, these swings typically occur every couple weeks, with the depressive state generally remaining for a more significant period of time. Although much more research needs to be done, scientists have begun to identify some of the potential neurological pathways that may be responsible for the drastic mood swings seen in those affected by BD. Although neurological degeneration is not one of the tell-tale signs of the disorder like many other neurological diseases, it has been suggested that excessive transmission of neurotransmitters such as dopamine and glutamate can set up conditions that lead to oxidative stress and cell death. Inflammation in the brain has also been identified as one of the main problems that can contribute to BD. At this point scientists are looking at mood stabilizers such as lithium, valproate, carbamazepine, and lamotrigine to treat BD, which may also help alleviate some of the problems caused by oxidative stress and inflammation.
Yet while research looks at drugs to treat BD, counseling services are still a great option for treatment of those with BD, especially for the depressive state. Unfortunately our society has placed such a negative stigma on counseling that at times you have to wonder if the benefit of the service is worth the scrutiny from society that comes along with it. We automatically characterize anyone going to a counselor as having a mental disease, something that can’t necessarily be treated with pharmaceuticals, or as being a crazy person. But what is a mental disease anyway? It seems as though anything that deviates from what society considers normal and balanced emotionally or behaviorally is now termed as such. And although I can’t say that having balance is a bad thing, I want to encourage everyone to be a little more understanding of those that seek out counseling as a way to feel relaxed and in control. Don’t get caught up in the labeling game that is played with mental disorders and deviations from “normal”. Personally, I can’t say that I’ve ever met someone who has their emotional and behavioral balance always in check. And if that’s the case, maybe we all have a mental disorder.
Bipolar Disorder: Why Aren't We Talking About It?
Psychological disorders, treatment and therapy to combat them, prescription medications…why aren’t we talking about it?
Reality slapped me in the face this week following my neurochemistry class in which we discussed bipolar disorder. I realized how much we as a society dislike discussing psychological disorders such as this very one. I don’t think that it is a stretch to say that we don’t recognize them unless there are visible manifestations of the damage such as shakes that appear with Parkinson’s disease, and memory loss in those who suffer from Alzheimer’s. But what about Bipolar disorder? Depression? Schizophrenia? Multiple personality disorder? All of these disorders are very real but perhaps not as easy to see on the surface. It is therefore easier to push them under the rug, which in my opinion is what we do as a society, even while people who are dealing with these diseases are struggling everyday.
I believe with the utmost importance that people need to be educated about psychological disorders such as bipolar disorder as being the first step in understanding how debilitating the disease is to those who suffer from it.
Bipolar disorder has an average onset age of 20, and is a psychological disorder affecting mood and actions. An individual who has been clinically diagnosed with bipolar disorder will cycle between manic and depressive states. The length of the cycles determines the type of bipolar disorder. In the manic state, which lasts for at least a week, the individual will experience symptoms such as high self-esteem, little need to sleep, constantly talking, irrational thoughts, distraction, or psychomotor actions such as pacing. On the other hand, during the depressive state an individual will have symptoms such as depressed mood, lack of interest, changes in diet and sleeping habits, lack of energy or even suicidal thoughts that lasts for at least two weeks.
Not much is known about the actual mechanism of bipolar disorder, but with a large amount of research having now been done on the subject, we are able to understand it better than ever before. There are findings in links between bipolar disorder and dopamine, glutamate and inflammation.
Dopamine is a neurotransmitter in the brain which plays a large role in reward-based behavior. In those with bipolar disorder, extensive dopamine release has been seen to lead to an increase in reactive free radical and oxidative stress. In simpler terms, free radicals are molecules that are highly chemically reactive, and too many of them can cause damage to cells in the brain, such as oxidative damage to DNA, lipids and proteins. The damage to these molecules can cause apoptosis (programmed cell death), cell membrane damage, and protein aggregation. Glutamate is an excitatory neurotransmitter and its increase can lead to an influx of Ca2+, which also causes oxidative stress as I previously described.
As for inflammation, there appears to be an increase in cytokines in those with bipolar disorder. Cytokines are pro-inflammatory molecules that modulate immune responses. This process is normally quite helpful with regard to our immune response, but research shows the process goes haywire in those who suffer from bipolar disorder. While inflammation in the brain has been identified in those with bipolar disorder, researchers are not completely sure on the inflammation process in its link to bipolar disorder.
Though many various drug cocktails are available to treat bipolar disorder, much more then determining the types of prescription medications to use needs to happen in order to understand this disease. I hope that in the future we are able to do much more to help people suffering from this debilitating disease, who need our understanding as much as our help. People with bipolar disorder might choose spend time in a therapist’s office discussing their condition, but there is no reason why we also can’t be there for them and discuss it outside of those doors.
Bipolar Disorder: Well, They Say Opposites Attract…
Bipolar Disorder: Well, They Say Opposites Attract…
It is human nature to display a range of emotions. As a college student, it is unwise to approach me in the morning immediately after I wake up because you will get the reaction of an unhappy, angry bear that has just woken from his slumber. But after a hot shower and some breakfast, I will be cheery and as friendly as ever. By the end of the school day, I will be antsy and anticipating the end of the day. When supper rolls around, I will be conversational and looking to ask how your day has been. Then darkness will set in, and I will be in a state of great focus until I can study no longer and must lie down to sleep.
These general changes in mood occur nearly every day; each person has his or her own individual manner and range of emotions. While these emotions are triggered by external events and internal thoughts, they are largely controllable based upon our own willpower, but most evidently, we are capable of recognizing these varying emotional states in which we might find ourselves.
On the other hand, there exists a commonly known disease called bipolar disorder. Although there is still much we do not know about bipolar disorder, we have classified it as one of many psychological disorders that can afflict our personality and behavior. Specifically, bipolar disorder is usually clinically diagnosed by the uncontrollable presence of varying emotional phases between which the patient cycles. These two phases include a manic phase where passion, energy, and goal-driven actions are intense and brilliant. Everything is over-the-top, and productivity can reach an incredible maximum. But, the manic phase tends to be somewhat short-lived; most patients with bipolar disorder spend the majority of their time in another state: the depressive phase.
In the depressive phase, one can imagine how this might look. If you simply imagine all associated factors with regular clinical depression, that about sums up the depressive phase of bipolar disorder. Oftentimes, patients with bipolar disorder understand that their brains chemically cycle between these two phases, but the transition between the two is not often as simple as flipping an on/off switch. And still, even if the patient recognizes that they are in the center of a certain cycle, they are powerless in attempting to act in a way that might counter the symptoms. For instance, if you had bipolar disorder and you recognized that you were at the peak of a manic phase after organizing your entire house in an hour, you could not simply tell yourself to “calm down” and relax to depress the manic phase because the chemical signaling in the brain cannot be overridden by your conscious thought. Similarly, telling yourself to be happy or to go for a walk in the park during a depressive phase simply will not magically transition you into a neutral or manic state.
Thankfully, there has been much research into the topic, and while I mentioned previously that there is still a large amount that we do not know, some light has been shed in relation to the disease. Originally, the focus in bipolar disorder was on a class of molecules called monoamines, but recently, new ideas have especially indicated the importance of inflammation, oxidative stress, and even some other common cellular processes.
Inflammation is generally characterized as an immune response which occurs through the use of molecules called cytokines. When a tissue is disturbed, (trauma, heat, infection, etc.) these cytokines are released, and they act as “targets” that attract white blood cells to the area. The white blood cells are part of your body’s immune response that can trigger inflammation and removal of infectious or problematic agents in your cells. Normally, this process is excellent and works to keep you healthy, but in patients with bipolar disorder, inflammation in the brain has been linked with their emotional phasic symptoms. Unfortunately, the cause of how inflammation is related to bipolar disorder is still unknown.
Oxidative stress is a very broad category that is usually associated with a cellular machine called mitochondria. Mitochondria are thought of as the “energy factories” of your cells, and just like any power plant or factory functions, they typically generate wastes while producing the energy that we need. In the same respect, mitochondria produce waste called reactive oxygen species. While reactive oxygen species are important in producing energy, if we have too many of them, they end up being toxic to many other functions in your cells and can cause other parts of the cells to become dysfunctional. I am sure you have heard of “antioxidants” in foods such as tomatoes or vegetables, but you may have not known that antioxidants are important because they get rid of these excess reactive oxygen species. Like inflammation, patients with bipolar disorder typically have irregular function of mitochondria, and therefore have problems with reactive oxygen species which lead to oxidative stress, but again, unfortunately, we have not yet uncovered exactly how oxidative stress is linked to the symptoms of bipolar disorder.
The crazy thing is that things like inflammation and oxidative stress are commonly found in a whole variety of psychological and neurological disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, and even have a link in head trauma like concussions! So then, the big question that scientists are working on answering is how many of these same irregularities that can occur in the brain will lead to the variety of vastly different clinical diseases. Clearly, there must be something different, otherwise the diseases would be the exact same. It will be very interesting to see within the coming years if we can tease out the subtle differences and begin to understand exactly what causes each of these separate diseases. Once we know this, I believe it will open floodgates for treating the true roots of these problems. Think of it this way: “If you have a leaky pipe, you can continue to plug and patch small cracks, but the best way to stop the flooding would be to simply turn off the water altogether…”
Final thoughts on bipolar disorder written by Steven Dotzler
Beyond the Shakes: Brain Pathology of Parkinson's Disease and Non-motor Symptoms
If you have ever witnessed someone with Parkinson’s disease suffering from tremors, it is a heartbreaking experience. To see someone trapped in a body they cannot control, unable to do anything but ride out the tides of tremors with no relief in sight, is absolutely gut-wrenching. It is difficult to imagine one day having a body that you cannot control, but for many, this becomes a reality as they age. Parkinson’s disease is the second most common neurodegenerative disease, with Alzheimer’s being the most common. It is characterized by a loss of motor control due to degeneration of dopaminergic neurons in the substantia nigra. This results in impaired motor functions that include: rigidity, tremors, bradykinesia (slowness of movement), as well as gait and postural changes. In addition to motor deficits, non-motor symptoms are also present in Parkinson’s, though research in this area is minimal.The presence of non-motor symptoms may come as a surprise due to the emphasis on motor deficits in PD. Less is known about the pathology of non-motor symptoms, but they can precede motor symptoms of PD by many years. Non-motor symptoms include: sensory abnormalities, autonomic dysfunction, cognitive decline, sleep disturbance, and depression. The frequency of non-motor symptoms increases with the severity of Parkinson’s, and they affect all PD patients.
In Parkinson’s disease, neuronal death occurs in various regions of the brain, not just the substantia nigra (the location of dopamine). The affected brain regions are pictured in the image above. Dopamine is the neurotransmitter involved in motor control and reward-motivated behavior. Degeneration of the non-dopaminergic areas of the brain is believed to be implicated in the onset of non-motor symptoms.
Here is a brief summary of the roles of the brain regions that degenerate in PD:
Substantia nigra: comprised of two parts, pars compacta and pars reticulata. The pars reticulata conveys signals to other brain structures. The pars compacta, the region that degenerates in PD, supplies dopamine to the striatum.
Non-dopaminergic Brain areas
Primary motor cortex: contains upper motor neurons that mediate planning and initiation of complex voluntary movements, receives input from substantia nigra
Locus coeruleus: largest group of of neurons involved in synthesis of norepinephrine, modulates circuits involved in attention, memory, emotion, stress, arousal, as well as posture and balance
Raphe nuclei: releases serotonin in the brain, helps regulate motor, somatosensory, and limbic systems
-low serotonin levels found in depression, damage to this area could be linked to depression observed in PD
Thalamus: involved in sensory perception and motor function regulation, receives sensory signals and projects them to the cortex, controls sleep and wake states
-degradation of this area impacts cognition, awareness, and perception
Amygdala: plays a role in processing memory and emotion
Hippocampus: involved in consolidation of information from short-term to long-term memory as well as spatial navigation
The presence of Lewy bodies is another defining characteristic of PD. Lewy bodies are abnormal protein clumps that aggregate in diseased neurons in PD. They are composed primarily of the alpha-synuclein protein, along with other proteins such as ubiquitin and tau. Lewy bodies build up inside the neuron and displace other parts of the cell, leading to cell death. Lewy bodies are found in the brain stem and deplete dopamine levels, and eventually spread to the other brain areas listed above.
Treatment of Parkinson’s disease is extremely difficult due to the complex pathology involved. Genetic mutations, excess glutamate, oxidative stress, and mitochondrial dysfunction are all contributing factors to neurodegeneration in PD.
The most common treatment of PD is the administration of L-Dopa, the precursor of dopamine, in an attempt to increase dopamine levels to help control tremors. It does help, but unfortunately, L-Dopa is not a cure-all. It cannot prevent neurodegeneration, and has averse side effects that include: nausea, hallucinations, confusion, extreme emotional states (especially anxiety), and insomnia, further exacerbating non-motor symptoms. We need more research into the pathology and onset of non-motor symptoms of Parkinson’s disease, as they often precede motor symptoms. Research into the pathology of non-motor symptoms is a viable outlet that could lead to new neuroprotective treatment strategies for Parkinson’s disease in the future.
This post was written in response to an article read and discussed in the Neurochemistry class at Concordia college.
The article can be found here: http://www.ncbi.nlm.nih.gov/pubmed/23380027
PD Brain pathology image retrieved from: http://stepsys.files.wordpress.com/2013/11/parkinsons-disease-204114724_std.jpg
Lewy body image retrieved from: http://www.cumc.columbia.edu/publications/in-vivo/Vol1_Iss19_nov20_02/img/LewyBody.jpg
The Mystery Named Parkinson's
Last week in neurochemistry we talked about Parkinson’s disease. This is a disease that has gained much popular attention in our culture due to celebrities and other famous individuals becoming diagnosed with this terrible disease. With as well known as this disease is, I thought that there would be well known mechanisms and pathways to how this disease manifests and can be treated. Normally, when a disease is this well known it is usually incredibly well funded—translating into research and a subsequent wealth of knowledge. Surprisingly though, researchers do not know very much about Parkinson’s. If you have been following along with our neurochemistry blogs you will have heard about how many of the neurological diseases that plague humanity boil down to oxidative stress, misfolding or tangling of proteins, and over activation by an excess of neurotransmitters. Many of those same factors come into play here and in Parkinson’s case the proteins of note include a-synuclein and parkin. Parkin is special in the fact that it is used as a cleaning crew for the cell.
In talking about this disease during a class discussion we came to a very interesting and difficult discussion. Throughout the semester we have examined many diseases where the physical capabilities of individuals are diminished, yet their mental faculties remain. We have also seen the exact opposite. An interesting question to ask yourself is which of these scenarios you would rather have.
When the death of Robin Williams occurred late this last summer, and when later details of his recent diagnosis with Parkinson’s disease and with depression I was given much to think about. When diagnosed with a terrible disease where you will slowly lose function is it an acceptable decision for an individual to end their life before their disease progresses? Imagine yourself on the deathbed or imagine watching a loved one slowly suffer themselves to death over the course of ten years. This shouldn’t be an easy question for you to answer, if it is I would ask you to think again about it.
The Hard Life with Parkinson's Disease
Working in the hospital has allowed me to care first hand for patients diagnosed with Parkinson’s disease. Parkinson’s is a very hard disease for a patient and family to deal with as it drastically changes the lifestyle of the patient as the disease progresses. I have seen families have to make many sacrifices to care for a loved one with Parkinson’s disease. I have also seen some of the sadness and frustration in the patient that can come from needing to ask help with meniscal tasks such as brushing ones teeth.
Parkinson’s disease is a disease that many people have heard about and can recognize some of the symptoms, but don’t fully understand what actually happens to a patient diagnosed with this disease. They believe it is a disease that affects the elderly by causing them to begin to shake uncontrollably until they can’t control their movements anymore. This is fair description of this unfortunate disease, but there is so much more to it than that. A lot of times it is misunderstood that Parkinson’s disease is something only the elderly get. As this is most often the truth, people as young as their mid 20’s can be diagnosed with early onset Parkinson’s disease.
Resent research has interestingly discovered that even though the disease isn’t caused by a virus or bacteria, it spreads from one region of the brain to next similar to how a virus would spread. Some of the implications of this is the disease starts in the area of the brain that involves muscle control. This is why some of the first signs of the disease is muscle spasms and shaking that progressively gets worse. As the disease moves to other areas of the brain it begins to affect mood and cognitive thinking. When the disease affects the mood areas of the brain it becomes especially hard to deal with because it can drastically change a patients behavior and personality, even causing depression.
So why haven’t we discovered a cure for Parkinson’s if we have been doing research on it for such a long time? Well as is the case with many neurodegenerative diseases, it seems as if multiple pathways go wrong at the same time and it is hard to pinpoint which pathway is initially causing the disease. Within Parkinson’s there is issues with the pathway that cleans up damaged molecules. There is also oxidative stress, inflammation, and mitochondrial malfunction. As it is hard to determine what is causing these issues the current method for treating the disease is to treat the symptoms described above, but this doesn’t ever slow the progression of the disease. Scientists have isolated a few mutated genes that appear to increase the likelihood of getting the disease, but are still working on developing a medication that could halt the progression of the disease.
The upside of Parkinson’s disease is that the life expectancy isn’t much less than that of someone without the disease. That doesn’t mean it isn’t incredibly difficult to live with, something that is clear to see whenever you observe someone struggling with the symptoms of the disease. It makes me happy to know that researchers are straining their brains to find a cure for this disease. Because of the difficulties that come with living with this disease, I hope that our advancements in technology will allow us to narrow in on a treatment for this disease in the near future.