Limiting Neurodegeneration in Parkinson’s Disease

Parkinson’s disease is a neurodegenerative disorder resulting in the loss of dopamine cells in the substantia nigra, which is responsible for reward and movement in the brain. Past research has incorporated L-DOPA, a dopamine precursor, that is used to increase dopamine levels within the substantia nigra and also slow the progression of stage one Parkinson’s disease. Researcher Ben Yang has a different approach in his research paper review, Calcium, Cellular Aging, and Selective Neuronal Vulnerability in Parkinson’s Disease. He believes that calcium entry into the cell through the L-type calcium Cav 1.3 channel causes oxidative stress in the mitochondria, which in turn create reactive oxygen species that trigger apoptosis in mitochondrial cells (Yang). These reactive oxygen species are also responsible for the dampening of ATP synthase and the mutations in mitochondrial DNA. When too much calcium enters the cytoplasm, it can create an aggregation of Lewy bodies within the endoplasmic reticulum indirectly or within the mitochondria directly. This aggregation of alpha-synuclein proteins (Lewy bodies) prevent the endoplasmic reticulum from undergoing proteostasis and restrict the mitochondria from utilizing energy efficiently (Yang). Yang’s solution to restrict the amount of calcium influx within the cell is to apply a hypertensive drug called isradipine, which also blocks calcium channels. Blocking calcium channels increases mitochondrial density in substantia nigra neurons, which creates a lower turnover in dopamine cells, causing dopamine neurons to age at a slower rate. Isradipine allows the substantia nigra mitochondria to produce less energy expenditure and prevents the formation of reactive oxygen species.

An article from ScienceDaily that ties in with Yang’s research, identifies the alpha-synuclein protein formation in brain cells and a way to block their action in the mammalian brain (John Hopkins Medicine). Ted Dawson, the director of Cell Engineering at John Hopkins School of Medicine, initially published evidence of alpha-synuclein spreading from areas of lower brain structures including movement to areas of higher reasoning and memory function. Building from this aggregation process, Dawson and his research team cultured human brain cancer cells that prevented the alpha-synuclein from entering the cell. The team then added genes to the transmembrane receptors of these cancer cells to see which genes let in the aggregates. Specifically, the transmembrane receptor called LAG3 bound to the alpha-synuclein aggregates (John Hopkins Medicine). The team then created knockout mice that lacked the LAG3 protein receptor and injected them with alpha-synuclein aggregates and sure enough, the neurodegeneration of dopamine neurons was limited by the mice antibodies. The mouse antibodies blocking alpha-synuclein aggregation had similar effects in cultured cancerous human cells and the antibodies are being tested in clinical trials. Thus, the blocking of LAG3 protein can possibly slow the progression of Parkinson’s in humans and be incorporated in chemotherapy, if the antibodies are approved in clinical trials. It seems that Ben Yang’s proposition of isradipine application to block L-type calcium channels aids in the durability of mitochondrial substantia nigra cells. Substantia nigra cells could then use energy in the form of ATP more efficiently and slow the formation of reactive oxygen species. Dawson and his John Hopkins research team’s proposal could possibly eliminate the formation of alpha synuclein aggregate. Both findings can play a part in regulating the neurodegeneration of dopamine neurons in substantia nigra cells.

Works Cited

Johns Hopkins Medicine. "New treatment strategy could cut Parkinson's disease off at the pass."            ScienceDaily. ScienceDaily, 29 September 2016.                       <www.sciencedaily.com/releases/2016/09/160929142756.htm>.

Ben Yang’s research review:            https://luc.app.box.com/v/neuroscienceseminar/1/5783518889/93009542353/1

Journal Reference:

Ted M. Dawson et al. Pathological α-synuclein transmission initiated by binding lymphocyte-  activation gene 3. Science, September 2016 DOI:10.1126/science.aah3374

Run Your Way To A Better Memory

So it’s the night before an exam and you’ve been studying all week for this behavioral neuroscience test. Luckily, it’s on your favorite chapter, the chapter on memory and you’ve been reviewing all of your notes and quizzing yourself for the past few hours now. Do you keep studying or do you go to bed or do you find something else to do? At this point you aren’t sure if cramming would even help or even if you could remember anything that you’ve been trying to study. Even your notes say so. You know that studying and learning new information takes time and that consolidation of the new memories needs to occur before they can become part of your long term memory. You decide to take a break and that it might not be such a bad idea to run off your anxiety at the gym for a bit before going to bed.

Surprisingly, that is the best thing one can do to promote memory consolidation and activate the neural pathways that are associated with better memory. In a journal article published in Current Biology, researchers brought in people for a memory study that consisted of three groups that either exercised immediately after, a few hours after, or not at all after partaking in a forty minute long picture-location memory task. The subjects returned to the lab two days after the task to see how well they retained the information they had learned and to get their brains scanned. What the researchers discovered was that people who exercised a few hours after the learning task had the best percentage of recall and out performed the groups that did not exercise and the group that exercised immediately after the learning task. Those that exercised a few hours after their memory task not only did better than the other two groups, but showed clearer activation in their brains in the areas that are associated with memory retrieval.

Other studies have shown that increased levels of the neurotransmitters dopamine and norepinephrine start the process which promotes the creation of plasticity related proteins, which in turn are associated with higher levels of cognitive function and memory. Physical activity and exercise promotes the release of dopamine and norepinephrine, which serve as the foundation of memory formation. Thus, it can be concluded that in conjunction with studying, exercise in healthy doses has the ability to help speed up the process of memory consolidation. So next time you are studying for an exam, it might not be such a bad idea to run from your problems. It might just actually help you do better on your exam than not.

Works cited:

Bridge, Donna J., and Ken A. Palmer. "Neural Correlates of Reactivation and Retrieval-Induced Distortion." Journal of Neuroscience. N.p., Aug. 2012. Web. 18 Oct. 2016.

http://time.com/4369529/exercising-after-a-task-improves-memory/?iid=sr-link1

Picture:

http://www.expertrain.com/blog/fitness/best-running-buddies.htm

Preventing Parkinson's Early

Parkinson’s disease is a neurodegenerative disease that affects people mostly over the age of 65. Chances of incidence continue to increase in developed countries due to increased life expectancy and rapid medical advancements. The disease continues to worsen over time and the cause of it is currently unknown, although there are many promising leads. It is well known that the brain’s dopamine producing cells are greatly diminished in those with PD and more correlations are being discovered to be linked to onset of the disease.

Quite recently, the role of mitochondria dysfunction has been linked to PD patients. It has been found that there is a substantial decrease in the activity of mitochondrial NADH ubiquinone reductase, which is complex I in the ETC. This inevitably results in issues with the electrochemical gradient across the mitochondrial membrane that aids in creating ATP, which we know is essential for all bodily functions. Genetics has also been playing a huge role in Parkinson’s research, as familial form of PD further point to the role of mitochondrial mutations and dysfunctions. The endoplasmic reticulum has also been heavily linked to PD and is responsible for production, delivery and degradation of proteins, notably Lewy bodies. Lewy bodies reflect the decline of proteostatic competence that accompanies normal aging, which is a huge factor in inducing Parkinson’s disease. There are also suggestions that Ca²⁺ plays a substantial role in onset of Parkinson’s disease and reducing the influx of Ca²⁺ should potentially slow triggering symptoms of Parkinson’s and slow its progression all together. All of these aspects linked to Parkinson’s are merely strong correlations. Even today, with advancements of medical technologies, the exact cause of the PD is unknown. The studies done on the involvement of mitochondrial dysfunction and endoplasmic reticulum are vital in better understand the molecular and cellular connections in patients with PD but they do not lead us to a cure.

To help the thousands of people with PD quickly and efficiently, other than treatment, greater significance should be placed on preventative measures. The only method that seems most appropriate in defeating this disease from our population is to find it early, before any irreversible damage has been done. Jane Brody, in her article “Looking for Parkinson’s Sooner Years”, describes the various signs to look for before the onset of PD. Those that eventually succumb to PD “have experienced tremor, balance problems, constipation, low blood pressure, dizziness, erectile and urinary dysfunction, fatigue, depression and anxiety” years before the classic symptoms such as rigidity and tremors.

In addition to those predictive signs, Brody’s article states that “REM sleep behavior disorder, characterized by a tendency to act out one’s dreams while asleep, is one of the strongest prediagnostic symptoms, along with a lost sense of smell and subtle changes in cognition.” This sleep disorder could affect thousands of people every year who eventually get diagnosed with PD. The first step in preventing the onset of PD is to acknowledge these underlying disorders that are strongly correlated with the disease. Brody mentions that up to eighty percent of those who have REM sleep behavior disorder get Parkinson’s or other neurodegenerative diseases. As soon as similar symptoms are observed, patients should consult with a neuro specialist to learn ways to prevent and delay degeneration while the brain is still mostly intact.Now that there are prediagnostic symptoms to look for that are quite common in the population, biomarkers are being studied to help identify likely PD patients. “Substances in the blood, saliva or cerebrospinal fluid or imaging characteristics” are the next step in preventing PD in those that are extremely high risk, as noted in the symptoms that occur years before the severe degeneration occurs.

Work Cited

Surmeier, D. James, Jaime N. Guzman, and Javier Sanchez-Padilla. “Calcium, Cellular Aging, and Selective Neuronal Vulnerability in Parkinson’s Disease.”Cell calcium 47.2 (2010): 175–182. PMC. Web. 19 Oct. 2016.

Brody, Jane E. “Looking for Parkinson’s Sooner.” Editorial. Nytimes.com. N.p., 15 Mar. 2015. Web. 19 Oct. 2016. <http://well.blogs.nytimes.com/2015/03/16/looking-for-parkinsons-sooner/>

Gestures!

What is a gesture? A Gesture is a simple movement of the hand that has the ability to convey a thought, idea or phrase that cannot be expressed using words. It is impossible to really know the amount of times we use these hand movements in a day. As a society we rely on these gestures to express our excitement over the weekend or our disappointment over an exam. They can carry the power to express the empathy we feel for others and the compassion we feel towards our passions.

  

In the article published by Novack, Wakefield, and Goldin-Meadow gestures are defined as movements that represent action, but, clearly states that in order to be classified as a gesture it cannot have an effect on the surrounding environment.  The article introduced to us by Dr. Wakefield clearly marks the differentiation between the acts of curling your fingers in a movement towards grabbing a water bottle, a goal directed movement, and curling your fingers in as an act of conveying a message in itself, a gesture. They discovered that this distinction can be noticed in infants as young as six month. Dr. Wakefield further touched on the notion that these babies at six months, however, were not sensitive to a change in the type of movement used with goal directed movement but rather there attention was drawn to a change in the goal itself. She then tested this effect on children later around the age of 10-11 months in which the reaction was provoked when the experimenters hand would stop before the object was reached but they would have no reaction after the goal oriented movement was completed. As the article continues we learn about the first study conducted by Dr. Wakefield to understand this differentiation between the movement and the action. She conveys this through the use of two studies. The first study consists of three conditions, the first in which the experimenter actually picks up the different colored balls and places them in the correct boxes, the second in which she does the movements but does not make contract with the items and lastly mimicking the movements without the objects present. The second study conducted focused on the context surrounding the empty handed movements in which she believed that the richer the context the gesture occurs in the more likely it is to be seen as a gesture.

The importance of these studies of gesture can be seen in the article published by Michigan State University based on the study in the Child Development journal. The use of gestures in learning was observed to have a positive influence on student’s ability to learn math. This conclusion came about through the use of two different videos, in which in the first one, the instructor only used speech to teach the lesson and in the second they used speech alongside gestures. The students were then followed up with a test in which it was determined that those who watched the video including gestures performed better than those taught just with speech. The test given also exposed that through the use of gestures the transition between concepts within math were more easily retained.

Seeing that simple movements of an individual’s hand can carry the power to influence future generations and facilitate better learning is necessity for every member of society. A concepts ability to influence development as well as learning both as an infant as well as an adult is fundamental to growth as well. 

Work Cited

Novack, M. A., Wakefield, E. M., & Goldin-Meadow, S. (2016). What makes a movement a gesture? Cognition, 146, 339-348.

University, Michigan State. "Teachers' Gestures Boost Math Learning."MSUToday. N.p., 29 Mar. 2013. Web. 20 Oct. 2016.

Image:

http://blog.deiricmccann.com/author/admin/. "GESTURES SPEAK LOUDER THAN WORDS." Deiric McCann. N.p., 09 July 2015. Web. 20 Oct. 2016.