Cobbers on the Brain – Page 127 – Student Commentary on the Neurological Sciences

Parkinson's Disease: Finding the Balance

Posted on February 16, 2016 by / 0 Comment

Merriam webster’s dictionary defines Parkinson’s disease as “a chronic progressive neurological disease chiefly of later life that is linked to decreased dopamine production in the substantia nigra and is marked especially by tremor of resting muscles, rigidity, slowness of movement, impaired balance, and a shuffling gait.”
A nice balance between dopamine and acetylcholine is key to motor control. Dopamine also plays an important role in many other bodily functions and neurotransmissions. For Parkinson’s disease the biggest issue is the imbalance between dopamine and acetylcholine, because of the decreased dopamine production.
Researchers so far have had a difficult time pinpointing what is causing the neuronal damage leading to Parkinson’s and other related diseases. Some environmental factors for Parkinson’s disease include increased age, being a male, head injury, occupation, area of residence, , pesticide exposure, exposure to metals, genetic predisposition, solvents and PCBs.
For a lot of these factors we can’t really do a whole lot until it is too late and the damage has already begun. These factors also don’t necessarily lead to Parkinson’s, but do increase your chances.
There is no way of getting around the fact that an increase in age will increase your chances of Parkinson’s and being a male will also increase your chances. Acquiring a head injury could lead to any number of related issues, but those are typically out of a person’s control. The occupation you choose could have some side effects that come with it depending on what you are exposed to. Jobs where you may be exposed to toxic chemicals and metals could increase your chances of developing disease.
Where you live could be a factor in your Parkinson’s chances. It could be environmental factors of the specific area that you live in, but it could also be related to the gene pool in your area. Maybe the fields around you are spraying pesticides or the place where you get your produce uses chemicals that could lead to an increased risk. Say you take away pesticides, then we have more of a risk acquiring an insect transported disease.
The Parkinson’s Disease Foundation also listed some potential protective factors. Caffeine, anti-inflammatory drugs, exercise, and vitamin D have been found to have positive effects on the brain. Some controversial protective factors included uric acid, taking drugs that lower your cholesterol, and nicotine.
Males with high amounts of uric acid tend to form kidney stones, but they also have an lower risk of developing Parkinson’s. If you have high cholesterol and take drugs to lower your cholesterol then you will have a lower chance of getting Parkinson’s, but your health wasn’t good to begin with because you had high cholesterol. If you naturally have low cholesterol your chances of developing Parkinson’s disease is higher. There has been a correlation between smoking and neuronal damage. Researches believe that nicotine may block the destruction of the neurons that leads to Parkinson’s.

Above is an artstract I drew to symbolize the effects of normal outside factors and some normal bodily functions that may be benefiting us, but could also be harming us.

These simple everyday factors are a lot like the proteins and enzymes in our body that we talk about in class. In one place they are doing a really great thing, but in another place they are destroying us. Why would our body be producing things that our toxic to us? With almost everything we do there are potential benefits and drawbacks. Our bodies weren’t meant to live forever and longer we live the more we are beginning to understand and fight that.

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The Imbalance of Parkinson's Disease

Posted on February 16, 2016 by / 0 Comment

Commonly seen in people over the age of forty, approximately 60,000 United States citizens are diagnosed with Parkinson’s disease every year. The magnitude of its affect along with its serious implications on the duration and the conditions of life give imperative reasons to understand this disease. While I do not believe medical practices should be catered to extending life, I do believe that modern medicine should seek to suppress its cognitive and motor affects. The only way to develop an affective treatment plan is to continue extensive research on the pathophysiology of this disease.

Characteristically, Parkinson’s disease causes the death of dopaminergic neurons in the portion of the brain known as the substantia nigra. Because of these neuronal deaths, patients suffer from dyskinesia which is the inability to control voluntary muscle contraction. Typically, patients display tremors, rocking back and forth, or fidgety movements. The real question, however, is what causes these neurons to die and why are these specific neurons affected?

It has been found through many neurodegenerative studies that the build up the protein, alpha-synuclein, is responsible for this dopamingeric neuronal death. Typically, this protein is found in the brain of healthy individuals, but at much lower concentrations. This is because the proteosome complex (proteins that breakdown other proteins) of healthy individuals use the enzyme Heme-oxygenase-1 to breakdown high levels of alpha-synuclein. In Parkinson’s disease patients, however, their brain has become resistant to this enzyme so there is no way to breakdown this protein leading to an aggregation of alpha-synuclein and eventually dopamingeric neuronal death. The use of heme-oxygenase-1 is a specific enzyme that is used in these cells to breakdown alpha-synuclein which leads to this neuronal specific cell death.

In order to suppress the impairment of Parkinson’s disease, it is essential to reestablish homeostasis in the part of the brain by degrading alpha-synuclein. Because of this, future research should focus on determining a reason why the brain becomes resistant to Heme-oxygenase-1 and develop a drug that could degrade this protein. If these goals were achieved, many friends, families, and patients would not have to go through the hardships caused by this disease.
As a student seeking a career in the medical field I think that focusing on this type of research would have many benefits to society as whole, not just those affected by Parkinson’s. This is because the knowledge gained in a study like this will take another step toward understanding the neurochemistry of the brain, hopefully leading to answers as to why these types of mutations arise in certain individuals. With this information we could better understand the impact of genetics and environment on neurodegenerative disease and help physicians detect and prescribe medications for these individuals. While I do not think we should seek to chase immortality, I do believe that as a society we should value the conditions of life and the complexity of our minds.

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Parkinson's Disease: Another Result of Brain Injury?

Posted on February 16, 2016 by / 0 Comment

I’m willing to bet that you have heard of the boxing legend Muhammad Ali. If you haven’t, I would definitely recommend watching some of the highlights of his illustrious career in the boxing ring. The guy was amazing. However, the guy also took some very heavy blows to the head throughout his time in the ring. That’s not surprising, though – boxing is an extremely brutal sport that comes with high risk of injury. But research into the neurological effects of traumatic brain injury suggest that this “injury” may be more than just a temporary painful experience. The unfortunate reality of Muhammad Ali’s life today is that he suffers from Parkinson’s Disease, or PD, and the connection between his diagnosis and history of boxing raises many questions.

What exactly is PD? It is widely known that PD is a progressive disorder of the nervous system that affects movement – a symptom that stems from the loss of dopaminergic neurons in the substantia nigra, a region in the midbrain. The role of abnormal protein kinase function, which leads to the elevated phosphorylation of the PD-defining pathological protein alpha-synuclein, has been implicated in having an effect on the loss of neurons. This depletion of neurons, shown in the picture below, leads to a decreased supply of dopamine in the brain, which is responsible for many functions such as movement control. Typically, PD patients exhibit this loss of control through slowed and jerky movements. This video shows the effects of PD on Muhammad Ali himself, in comparison to before he developed the disease.

But why did he develop PD? Could there be a connection to the years and years of taking punches to the head? Researchers at UCLA have done extensive work on traumatic brain injury (TBI) and its connection with the development of Parkinson’s Disease (PD). They have found that having experienced a TBI doesn’t necessarily cause PD, but dramatically increases the risk of developing the disease. One of the researchers leading the study explained that, “With a moderate traumatic brain injury, the loss of neurons was too small in number to cause Parkinson’s disease, but it is enough to increase the risk of PD. By decreasing the number of dopaminergic neurons, any further insult to the brain will be attacking a smaller number of neurons; as a result, the threshold for symptoms would be reached faster.”

In the long-term study, found here, the rats’ brains showed a 30 percent loss of dopaminergic neurons 26 weeks after the injury. This finding suggests that traumatic brain injury alone is sufficient to induce a progressive degeneration of dopaminergic neurons in the long term. Additionally, this research supports the finding that with a first moderate brain injury, the susceptibility to another increases drastically.

Isn’t this a scary thought? Not only does an injury to the brain lead to immediate effects such as concussion development, but it can also lead to the loss of neurons responsible for coordinating muscle movement in the body. And with the buzz surrounding the concussion policy of the National Football League as well as the seemingly endless cases of chronic traumatic encephalopathy (CTE) former NFL players have developed, it seems that the impacts of brain injury are even more severe than previously imagined.

Disease/Health

Is Deep Brain Stimulation the New Face for Parkinson's?

Posted on February 16, 2016 by / 0 Comment

In the United States, more than 200,000 people are affected each year from Parkinson’s disease. As much of the general public knows, this disease is a debilitating neurodegenerative disease that often is diagnosed after the age of 40. That being said, what many people don’t know is that the symptoms that they associate with Parkinson’s disease may not be from the actual disease itself, but rather the medications individuals are taking. Possibly the most recognizable characteristic of advanced Parkinson’s is dyskinesia, or involuntary motor movement that can been seen as body tremors, rocking back and forth, or just the inability to sit still. Surprisingly, this hallmark of the disease often is the result of high doses of drugs derived from the compound called L-DOPA.

What We Know about Parkinson’s

Truly, the symptoms in the disease’s original state are slowness of voluntary movements, a shuffling gait, abnormal stiffness, and poor balance. These are the result of the death of dopaminergic neurons in an area of the brain called the substantia nigra. In Parkinson’s disease, the leading theory is that this cell death is caused by the build-up of an activated protein called Alpha-synuclein. Little is known about why this activated protein builds up in dopaminergic neurons, but extensive research is being done on kinase dysfunction that could lead to the buildup and subsequent cell death. Knowing that activated Alpha-synuclein is likely the cause for the dopaminergic cell death in Parkinson’s disease, there is also clinical research focused on targeting the Alpha-synuclein, including vaccines and compounds that can break down the protein.
In past and many current treatments for Parkinson’s disease, the goal has been to supplement dopamine for the brain to try and compensate for the death of these neurons. Dopamine drugs, including L-DOPA, serve this purpose well. This drug has the ability to flood the brain with dopamine, but unfortunately, patients taking high doses of this drug have to live with the side effects such as the inability to sit still.

Where Deep Brain Stimulation Fits in

This is where deep brain stimulation (DBS) may be the key for some Parkinson’s patients. The goal of this procedure is to regulate the “on/off” characteristics of the disease and help reduce dyskinesia. In DBS, a thin electrode is implanted into the brain, targeting motor circuits that are not functioning properly. Small electrical pulses from a device similar to a cardiac pacemaker are then used to stimulate a small brain region and block the signals that cause some Parkinson’s symptoms and symptoms from L-DOPA drugs. DBS may not be the answer for everyone, but studies have shown that is works best for patients who respond well to dopamine drugs but just suffer from their side effects. Just as with any other medication or procedure, this treatment should be approached with realistic expectations and understanding of the risks associated.

For me, as a student infatuated with research and its clinical applications, this is extremely exciting; but I think this also should be exciting for everyone. Deep brain stimulation may be a way for people suffering from Parkinson’s to experience the relief from drugs such as L-DOPA, but also live a life not hindered by its nasty side effects such as dyskinesia. With this brain treatment, before research is developed enough to effectively target the Alpha-synuclein and find a cure, there is a possibility that people with Parkinson’s may have the ability to be just another face in the crowd.

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Stem Cells and Parkinson's Disease

Posted on February 16, 2016 by / 0 Comment

Stem Cell Research has been the on the cutting edge of science, and become extremely useful for many neurodegenerative diseases like Parkinson’s Disease.
Parkinson’s disease (PD) is a common neurodegenerative disorder, defined by a selective loss of dopaminergic (DA) neurons in the substantia nigra, and the formation of lewy bodies. While common signs and symptoms include tremors, slowed movement, rigid muscles, and impaired balance, non-dopaminergic symptoms can include gait abnormality and dementia when the disease spreads to non-dopaminergic systems, and these can be increasingly challenging to treat. 60,000 American’s are diagnosed with Parkinson’s each year, with an estimated 10 million people living worldwide with this condition.
Recent research on Parkinson’s has concentrated on dissecting the neurological mechanism in order to discover therapeutic strategies. Protein breakdown, mitochondria dysfunction, oxidative stress and kinase pathways are implicated in PD, with many cellular and animal models having been established to unravel the mechanism behind PD. However these discoveries are not based on human neurons, and may not reflect several disease-causing factors present in human Parkinson’s disease.
Stem Cells
Stem cells are a growing field or research, and are a renewable source of tissue that can be coaxed to become different cell types in the body. The best-known examples are the embryonic stem (ES) cells found within an early-stage embryo. These cells can generate all the major cell types of the body. This form of research has drawn ethical concerns throughout the media for years, with the concern of abusing a potential human life form. However research involving Parkinson’s Disease and Stem Cells do not use this form of research, averting ethical concerns with regard to fetal tissues. Induced pluripotent stem cells (iPSCs) refer to a group of pluripotent stem cells that can be generated from adult cells. These cells share the same property as embryonic stem cells, to be able to differentiate into any tissue in the body. Numerous terminally differentiated cells can be used to generate iPSCs, avoiding destruction of an embryo. Sources of iPSCs include skin, liver and stomach cells. New breakthroughs in iPSCs include potentially programming iPSCs from a follicle of hair or a mouth swab.

Contributions of iPSCs
iPSCs have provided the opportunity to understand the PD mechanism in more detail, by doing pathological studies on live DA neurons. For example, a large break-through via iPSCs have connected mitophagy with PD. This complex mechanism involving PINK1 and Parkin enzymes has further cleared the event of decreased mitochondrial regulation with Parkinson’s Disease.
Therapeutics have also been developed through access of iPSCs. Coenzyme 10, rapamycin, and LRRK2 inhibitor are drugs found to alter cytotoxicity in neurons from patients with PD. Furthermore, it was found that these medications selectively reduced oxygen species production in neurons with the PINK1 mutation, clarifying the difference in susceptibility between diseased neurons and artificial disease models.
iPSCs have contributed to diagnosis methods. iPSCs derived from patients may serve this need if the phenotypes shownin iPSC-derived neurons exhibit pathological features in PD. This has further improved diagnostic accuracy of early PD.
Recent research has yielded encouraging results regarding cellular replacement. Some recent attempts transplanting dopamine neurons from rodent to primate was successful and produced increased cognition. Additionally, it was found iPSCs were able to differentiate into dopamine neurons and rescue motor deficits in a rat PD model. This was also repeated in a primate. Although this is relatively unexplored, these results provide a favorable outlook for the application of transplantation of iPSCs for PD treatment.
Overall, iPSC-derived neurons provide promise for PD modeling, and can be utilized for investigation of disease pathogenesis, diagnosis tools, and offer new therapeutics for patients.

Disease/Health

Parkinson's Disease Today

Posted on February 16, 2016 by / 0 Comment

When most people think of Parkinson’s Disease (PD), they may think of Micheal J. Fox or Muhammad Ali and their symptoms of jittery and slowed movements. Other symptoms include tremors, rigid muscles and impaired posture and balance.
They might not even think about the potential causes behind one of the most common neurological disease. PD is defined as a progressive disorder of the nervous system that affects movement. Individuals are usually diagnosed with PD around the age of 60.
The exact cause of PD is not known, but researchers have shown great interest in alpha-synuclein for playing a role in PD. Alpha-synuclein are proteins in the brain, their functions are still unknown.
The clumping of these alpha-synuclein form Lewy Bodies, which are toxic and lead to cell death. As they accumulate throughout the brain, the number of dopaminergic neurons decreases in the substantia nigra. The lack of dopaminergic neurons causes the motor issues associated with PD.

Other hypotheses for the loss of dopaminergic neurons include inflammation, autophagy, protein aggregation, mitochondrial dysfunction and oxidative stress. A number of different kinases in these various biological processes can alter their functioning and cause the accumulation of alpha-synucleins.
New clinical trials of assorted treatments have been shown to decrease the number of Lewy Bodies. A vaccine approach targets alpha-synuclein and clears it from the brain. While other treatment methods have been shown to stop the clumping of alpha-synuclein, and break up existing clumps. These treatments show promise for curing a harmful disease.
It is estimated seven to 10 million people in the world have PD, and about 60,000 Americans obtain PD each year.
By continuing to examine different factors that may cause PD and continuing to push clinical trials for effective treatments. It will allow researchers to potentially find the cause of PD, and obtain a cure for it.

Disease

Diagnosing Parkinson's: Not So Straightforward

Posted on February 16, 2016 by / 0 Comment

What is Parkinson’s Disease ?
The Mayo Clinic defines Parkinson’s Disease (PD) as a progressive disorder of the nervous system that affects movement. Symptoms include tremors, slowed movement, rigid muscles, impaired posture and balance, loss of automatic movements, speech changes and writing changes. The “simple” cause of these symptoms is the loss and death of neurons, however what is causing the death of neurons is a question scientists have been trying to figure out for decades.
What really causes the symptoms?
To put it into simple words researchers have been able to “pin point” the cause of PD to dysfunctional protein kinases. Protein kinases are enzymes found within the brain and they work by adding phosphate groups to other enzymes with specific functions. By adding a phosphate group kinases cause the other enzyme to either do their job or cause them to stop doing their job. I put quotations around “pin point” because there are a MANY protein kinases within the brain and some have very strong links to PD while others not so much and it seems like new kinases are being linked to PD left and right. To complicate things further these kinases can have VERY different functions in the brain. Most commonly, dysfunctional kinases that are linked to PD deal with oxidative stress, inflammation and autophagy in the brain. Autophagy is a normal process where cells essentially clean up old and used up proteins.
How do we diagnose it now?
With so many kinases linked to PD doctors cannot just look at the levels of some protein in the brain and say with certainty a patient has the disease. Currently the only approved way of diagnosing PD is by looking at symptoms and ruling out other diseases that could cause similar symptoms to PD. I found on the Mayo clinic website that if doctors suspect a patient has PD they can administer a drug used to treat PD and if improvement of symptoms follows that patient most likely has PD.
Are there other ways to diagnose PD?
I found two articles that described some interesting new ways to potentially diagnose PD. The first was about Oxford University researchers that used a new MRI approach called resting-state fMRI. This technique looks at the strength or connectivity of brain networks. The researchers focused on the basal ganglia a part of the brain known to be affected by PD. Using this technique researchers were able to get a correct diagnosis 85% of the time. The second article I found on BBC news told the story of a woman who claimed she could diagnose PD by smell. A researcher got wind of this and put her to the test. Using 6 PD patients and 6 control subjects, people without PD, the researchers had each subject wear a shirt all day and then kept them for testing. They had the woman smell each shirt and she got 11 out of 12 correct. There was one control subject that the woman was sure had PD however the patient claimed to not have PD and doctors did not diagnose this either. However, 8 months later that subject was diagnosed with PD! Meaning this woman was actually 12 for 12!
These novel ways of diagnosing PD are not used widespread what so ever but, could potentially be in the future.

Disease/Health

Adult Stem Cells: A Potential Treatment for Neurological Disorders

Posted on February 16, 2016 by / 0 Comment

With greater detection potential and the ever-increasing average age of citizens in the United States, neurological disorders are increasingly diagnosed in our country and their effects are gaining national attention. Parkinson’s disease, by itself, has been diagnosed in as many as one million Americans with approximately 60,000 new cases arising each year.
While the impact of Parkinson’s disease is felt all over our society, there is a real lack of understanding of what exactly this disease is and what causes it.

http://www.buzzle.com/articles/function-and-location-of-substantia-nigra.html — Location of the substantia nigra within the brain

The characteristic effect in Parkinson’s disease is the loss of specific neurons that synthesize dopamine (a neurotransmitter). These neurons are located within the mid-brain at a location called the substantia nigra. Dopamine signalling within the substantia nigra controls smooth motor movement and so dysfunction in this area leads to the jerky motions that are commonly seen in Parkinson’s disease.
What causes these cells to die is still somewhat unknown although a few mechanisms appear to be favored in terms of explaining the pathology of Parkinson’s. Aggregates called Lewy bodies which are made of malformed, clumped proteins are found within the dopamine neurons and create inflammation eventually leading to neuron death.

Whether these protein aggregates are created by overactive enzymes, genetic abnormalities, or environmental factors is still uncertain, but there is a new type of treatment that looks promising for treating neurological disorders such as Parkinson’s.
Unlike embryonic stem cells, adult stem cells arise from a mature cell that researchers have been able to induce into a embryological state. These stem cells, also called induced pluripotent stem (iPS) cells mimic the ability of embryonic stem cells to replicate and diversify into functional, healthy cells of all types and can be used in replacement therapy or as a means to expand research possibilities.
In recent research, iPS cells demonstrated the ability to develop into healthy tissues like dopamine neurons and could potentially be used as a novel treatment for Parkinson’s disease.
Stem cells could revolutionize our treatment of disease as regrowing completely healthy tissues falls within our grasp. The future is much closer than it seems.

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The Parkinson's Brain

Posted on February 15, 2016 by / 0 Comment

This week in Neurochemistry class, we talked about one of the many mysterious neurodegenerative disorders; Parkinson’s Disease.
I like to think of the brain as an orchestra, and Parkinson’s as a conductor with a terrible sense of time.

Normally, the conductor guides the orchestra through their music, producing a smooth, synchronized sound (coordinated movement).
However, the conductor of someone with Parkinson’s is unable to keep their orchestra on the same page—the music stutters, stops, and lags. Unfortunately, no one knows why the conductor is having these issues.
Some musicians give up and leave the concert (neuronal death), and the ones who think “The show must go on!” stay and try to compensate for the missing instruments (the excess firing leading to jerky movement).
Current research is trying to figure out what is causing the conductor to lose their ability to coordinate the band. What causes it? Is it related to age? Is it related to diet or head trauma?
That’s the thing; no one knows.

We talked a lot about what potential causes of PD are, but really, the class left me with more questions than answers.
It was very beneficial for me to understand the different things that may cause Parkinson’s. It made me understand that even though we are still a long way away from fully understanding this disease, we are a lot further along than I had known.
As we all know, the brain is the most complex piece of machinery on this planet. There are so many different reactions going on in our heads it is hard to imagine that errors such as PD only happen in about seven to ten million people worldwide (which is only about 1% of the entire world’s population).
But, why does this matter? What’s the big deal about Parkinson’s?
Well, it’s a big deal because not only are brain cells dying in certain areas, but those diagnosed are more cognitively aware of what is happening compared to those with Alzheimer’s.
Unlike Alzheimer’s and much like some cancers, patients with PD are fully aware that they are losing their ability to control their movement, which will impact their independence and ability to communicate.
Although it does not affect most of the population, it is important that we help those that are affected by understanding the disorder.

Parkinson’s is a neurodegenerative disorder that involves the loss of ability to coordinate movement, which is why one of the stereotypical symptoms of PD is jerky movements. Some people who are affected have trouble walking, sitting, and even talking.
The neurons that are dying in the brain are causing this effect. The death is occurring in specific areas of the brain that are associated with movement. The problem is, as I’ve mentioned before, we don’t know what is causing these cells to die exactly.
Studies have found many links to neuronal death, such as excess “bad” proteins in cells, too much activation of particular cells, causing overexcitation and then death, etc, but an answer is still unknown.
Each research study is getting us one step closer to determining how to prevent, treat, and cure Parkinson’s by figuring out how to get the brain’s conductor back on track.

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We need to talk about Cannabis

Posted on February 10, 2016 by / 0 Comment

Cannabis, also known as Marijuana, is a flowering plant most famous by its use as a recreational drug. However, the Marijuana medical use was described in many different cultures, including Ancient China, Ancient Egypt, and Ancient Greek. Over the years, Marijuana recreational use became illegal, as well as the medical use. Recently, the Cannabis medical use became a hot topic, due to several studies revealing positive outcomes.
The medical use of Marijuana has been studied due to its composition: it contains cannabinoids, chemical compounds that bind to cannabinoids receptors in the brain releasing neurotransmitters, leading to numerous chemical reactions. Those cannabinoids present in Marijuana can substitute endocannabinoids, cannabinoids that are naturally produced by our body and are involved in a variety of physiological processes, such as memory, appetite, response to stress, immune system, etc.
The benefits and detriments of Marijuana need to be further studied, but today the Drug Enforcement Administration classifies Marijuana as schedule I drug. What does it mean? “Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. Schedule I drugs are the most dangerous drugs of all the drug schedules with potentially severe psychological or physical dependence.”
This classification makes difficult to researchers to obtain legal supplies in order to better understand how Marijuana can be helpful (or not) for patients suffering from cancer, AIDS, epilepsy and other diseases. Today Marijuana medical use is legal in 23 states, but there is much more to be done. It is urgently necessary to allow and facilitate the research involving Marijuana, so scientists can determinate the benefits of the plant, in order to develop novel treatments to diseases that affect thousands of people. The better understanding of how Cannabis affects our brain would also give a stronger base for its legalization and regulation.
Cannabis legalization must be discussed, not just looking to the recreational use side, but looking especially to the medical use and research side.