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March 14, 2020

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February 28, 2020

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February 6, 2020

Nursing Research and Neuroscience


Neuroscience is certainly one of the most complex areas of medical practice. More emphasis is given to the field compared to other areas.

But did you know that nursing has an important role to play in neuroscience? The two cannot be separated. This makes it important to evaluate different nursing research areas.

What nursing areas do you think could the most pertinent when it comes to neuroscience?
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December 5, 2011

A Terrible Mistake Has Been Made


Human Immunodeficiency virus (HIV) today has been wrecking the lives of the people today. Categorized as one of the top world killers in the world, scientists have worked hard to find the cure. For those who are patiently waiting for a cure, many participate in CARTs or combination antiretroviral therapy which uses the combination of different antiretroviral drugs to stop HANDS or HIV associative neurocognitive disorders. Patients participating in this therapy were found to experience increase damage to brain. It was concluded the therapy is not an effective way to combat HANDS. Mihyun and her team exposed hippocampi of rats to gp120 for different lengths of time, than inhibited suspected proteins of the pathway such as CXC4R and then viewed the results with Open Lab software and calcium imaging.

Gp120, a surface protein that functions to bind to T-cells, is a toxin that enhances NMDA activation, but how, no one knows how. Studies found by disrupting the trafficking of NMDA resulted in disorders such as Alzheimer's. Evidence suggested that gp120 assembles NMDA receptors into clumps or modified microdomains. This occurred by increasing the size and stability of lipid rafts which are involved in receptor trafficking. Mihyun and her team used this theory as a baseline to discover the mechanism.

The team was successful in finding a mechanism. First gp120 enhanced the transport of NMDA receptors into the membrane by signaling phosphorylation of the C terminal which regulated transportation of NMDA. Exposure of gp120 to the hippocampi was found to increase the levels of phosphorylation, specifically phosphorylation of serine 897 and serine 896. Finally inhibition of PKA or PKC resulted in halting gp120 activity. PKA and PKC were thus concluded as the kinases activated by gp120 to phosphorylate the C terminal.

Then gp120 stabilized NMDA receptor microdomains by increasing the size of lipid rafts. Ceramide, a substance used by lipid rafts, was believed to be involved in increasing the size and stability of lipid rafts. Ceramide is synthesized by hydrolysis of sphingomyelin, a type of lipid. By blocking hydrolytic pathways in the hippocampi, the lipid rafts were observed not to be increase in size. In particular the enzyme nSMase2 which hydrolyzes sphingmyelin, was found to be the one responsible for increasing lipid raft sizes. Mihyuan took this further and inhibited key factor from a separate pathway that also increased lipid rafts. CXCR4, a protein that HIV uses, was found to increase lipid rafts with the use secondary messengers called IP3 and PKC.

Finally Mihyun and team found that by stabilizing the lipid rafts, NMDAR receptors were prevented from dispersing from the microdomains. Gp120 were first exposed to hippocampi then exposed to Beta cyclodextrin, a drug that is used to disrupt lipid rafts.
Mihyun and her team had made a great contribution which will has brought us one step closer to finding a cure. Though it may seem like only a baby step, at least we are one step closer.

Bae, Mihyun, et al. "The Human Immunodeficiency Virus Coat Protein gp120 Promotes Forward Trafficking and Surface Clustering of NMDA Receptors in Membrane Microdomains." The Journal of Neuroscience 31.47 (2011): 17074-17090
Posted by      Erika L. at 8:31 AM MST
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October 24, 2011

Restoration of Bovine Sanity and a Cure for Neurodegeneration


Mad cow disease. This deadly, presently incurable, brain-eating disease has been the cause of many a steak-lover's trepidation. After all, who wants his brain looking like swiss cheese? It is caused by the consumption or spontaneous generation and accumulation of PrPSc - the misfolded form of cellular prion protein (PrP) - and is responsible for several forms of "swiss cheese brain" besides bovine spongiform encephalopathy (affectionately known as mad cow disease), including the sheep-transmitted scrapie and the human form known as Creutzfeldt-Jakob syndrome, among others. Unfortunately for its victims, PrPSc is much more stable than the properly folded form of the protein and is thus resistant to normal methods of protein digestion (i.e. with protease) and is only known to be degradable via incineration of the infected victim. Clearly, this is an undesirable outcome for the individual who has been unfortunate enough to come into contact with such a protein.

As the misfolded PrPSc aggregates, it forms amyloid fibrils, essentially converting the normally folded PrP to the dark side and eventually causing neuronal cell death and ultimately the death of the organism. However, a recent study of methods to stabilize mouse PrPSc species, published in the Journal of Neuroscience, has shown that prion activity can be reduced by trapping partially digested PrP(27-30) with thienyl pyrimidine compounds.

The process of PrP conversion to the abnormally β-sheet-rich PrPSc form is autocatalytic, that is, it happens spontaneously and independently of other types of molecules. In their study, the researchers discovered that the formation of amyloid fibrils may actually be the "result of a protective process to sequester more dangerous soluble oligomers". As a result, rather than attempting to break the prions apart into smaller, supposedly more easily digested pieces, they decided to attempt to isolate them to avoid increasing the infectivity. Using mouse neuroblastoma cell cultures, they performed various drug assays and blotting techniques, including incubation of fibrils with thienyl pyrimidine compound. When all was said and done, they only observed a minimal decrease in the rate of infectivity, but it was a decrease, nonetheless. They concluded that the binding of thienyl pyrimidine-based drugs diverted dimers and trimers of misfolded protein from their pathological aggregation pathway, trapping them thermodynamically in an energy valley where they could no longer fold into their mortality-causing fibril-forming shape.

Though the study was largely inconclusive, it is clear that meaningful advances were made in discovering that the treatment of prion diseases is not as hopeless as we have believed up to this point. Indeed, the thought of finding a cure seems a daunting task, as the mad cow protein only seems to become more stable under most reaction conditions. However, this study has shown that sometime in the not-so-distant future, the mechanism of misfolding will likely be discovered, a cure for a once incurable disease developed, and we will no longer have to fear prions as much as we have in the past. Also, not only does this research have significant implications for those of us who enjoy a good steak or lamb chop, it may also have far-reaching influence on the treatment of other "prionopathies", including Alzheimer's, Parkinson's and Huntington's Diseases. Since these are diseases which affect a significant fraction of the aging population, research in this vein is critical for the progress of gerontological studies as well.

http://www.jneurosci.org/content/31/42/14882.full
Posted by      Clarinda H. at 12:03 AM MDT
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October 23, 2011

The Better to Remember You With, My Dear...


We've all heard those reports on "super fruit" or the next magical food to prevent this disease or to cure that disease during slow news days. While these stories are lovely fluff pieces, they often lack substantial support. Fortunately, a group of neuroscientists took it upon themselves to perform a legitimate study and to pull information from reliable research in order to identify certain foods that may be helpful in fighting the curse of aging, as well as pinpoint the beneficial effects of these dietary components.

The studies revolved around prevention and possible therapeutic techniques for neurodegenerative diseases and the aging of the brain in general. The first substance of focus was polyphenol, found most often in berry fruits. During experimentation on rat subjects, there proved to be a significant improvement in motor abilities in the group receiving a diet rich in polyphenol while the abilities of the control group either
deteriorated or maintained. In the experimental group, there was also an improvement in various aspects of memory, including LTP, fear conditioning, and both hippocampal-dependent and striatum-dependent memory. It is believed that the reasons for these enhancements are not only the antioxidant activity of the fruit, but also the positive effects on neuronal communication, a neuron's ability to buffer against calcium, and lessening of stress signals. Polyunsaturated fatty acids found mainly in walnuts have been found to improve age related motor and cognitive declines, too.

The article makes it clear that two important factors of the negative effects of aging are oxidative stressors and inflammatory issues. While not much is known about the specific mechanisms that these compounds work on, it is inferred that one of the reasons that they are so beneficial is because of their ability to reduce oxidative stress. Oxidative stress could cause disruptions in the balance of cellular calcium and could cause issues in neuronal signaling. Furthermore, high levels of oxidative stress can ultimately cause gene expression to be changed which could have drastic effects on the dynamics of individual cells, as well as the function and interaction of large groups of neurons. Docosahaenoic acid, or DHA, contained in walnuts and fish oil also plays a large role in the positive activities of these foods. DHA has been linked to anti-inflammatory properties that work to prevent Alzheimer's Disease. It seems that DHA is able to reduce Aβ oligomer production which in turn reduces toxicity levels within cells.

The disadvantages of the use of these foods are heavily outweighed by the advantages. The principal disadvantage stated in the article is the fact that relying on these foods to prevent neurodegenerative diseases could be hard to stick to because of the lack of variety. That is obviously dwarfed by the advantages brought up in the study, a few of the obvious being "safety, broad spectrum utility, low cost, and suitability for prevention." Giving up variety in order to delay ailments such as Alzheimer's Disease and Parkinson's Disease is a minor drawback.

Source:

Joseph, James, et. al. Nutrition, Brain Aging, and Neurodegeneration. The Journal of Neuroscience. 29(41): 12795-12801. < http://www.jneurosci.org/content/29/41/12795.full?sid=8a55155f-f531-41b3-90f4-e52fceaf9313 >
Posted by      Breanna S. at 12:19 PM MDT
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Posted on Mon, 24 Oct 2011 6:20 PM MDT by Christina U.
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July 31, 2011

What Does a "Senior Moment" Really Imply?


How many of us have been wary of getting into a conversation with a senior citizen because it may take too long and we are in a hurry? When an older person can't remember a name or a specific event, how often does someone think that that person has Alzheimer's or dementia? Why is it that seniors do not get the benefit of the doubt that their brains may be working, just a little bit more slowly? It seems that our society needs to take into account that seniors? brains do experience a certain amount of decline, but that doesn?t mean that the person is losing their mind.

It is a well known fact that as people age they will have trouble remembering to some degree, but how much of that is normal aging and how much is Alzheimer's Disease. It is common to hear about sons and daughters getting frustrated with their older parents when they forget an appointment or a name. The children will have concerns that their parents are getting Alzheimer's. How much of that forgetfulness can be attributed simply to aging? The distinction between normal aging and dementia has always been fuzzy, until just recently.

Dementia, especially Alzheimer's Disease, has been the main focus of gerontological neuroscience for the purposes of diagnosis and treatment. Just recently, a new focus of neuroscience has been to look at what is normal aging for the brain. Through a battery of studies and tests, there seems to be some understanding of what happens to the brain during normal aging.

Long-term memory is one of the most well known types of age related cognitive decline. The left inferior prefrontal region shows less activity in seniors than in young adults during memory tasks. The activity level in this brain region could be increased with cues and "encoding strategies" (Park & Reuter-Lorenz, 2010). Another one of the main deficits that is associated with aging is a decrease in cognitive speed in memory retrieval. This has been shown to be associated with decreased axonal volume or white matter volume (Park & Reuter-Lorenz, 2010). The implications of the research on cognitive speed could be as simple as wait and give them time. There could one day even be a pharmacological treatment that combats the decrease in white matter volume.

There seems to be a simple way to combat some of the decline in the aging brain. Park and Reuter-Lorenz were able to find that "investments made earlier in life, in the form of intellectual, social, and physical enrichment, may increase neural reserve and potential for effective scaffolding as people meet increasing challenges later in life" (2010). With that said, living a rich and thought provoking life in all the above mention areas of life may lead to brain structure that can withstand the negative effects of aging on the brain.

These advances in research could be monumental for every aspect of a senior's life, such as visits to the doctor, daily interactions, and even long term care. Medical care can be simplified by the simple understanding that cognitive deterioration is automatically Alzheimer's Disease or another form of dementia. If a person exhibits normal cognitive aging, a doctor trained in neuroscience would know not to automatically medicate that individual. The doctor would know to educate the senior and his or her family members about ways to better function everyday, like using the cues and encoding strategies. Seniors with normal aging entering long term care would benefit because the care staff would have a better understanding of how to care for them after becoming educated themselves or consulting with the doctor.

The huge advances in gerontology and neuroscience have allowed us as a society to gain a better understanding of what is going on in our grandparents' brains. It has also allowed us to extend the research and the possible benefits to areas outside gerontology to help the entire lifespan.

From the paper by Park, D.C., Reuter-Lorenz, P.A. "Human Neuroscience and the Aging Mind: A New Look at an Old Problem" in Journal of Gerontology.
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