Microglia will be isolated from C57BL/6 mice and infected with WT EEEV and mutant EEEV. qRT-PCR will be performed for EEEV mRNA levels at 6, 8, 12, and 24 hours. RAW.297 monocyte/macrophage cells or BHK-21 fibroblasts will be used as controls. We will also knockdown miR-142-3p using a miRNA sponge as described previously. Flow cytometry will be used to measure the proliferation of microglia in both infected and non-infected cells, and quantify the expression of effector cytokines IL-6, IL-12, IL-16, and IL-23. We predict that high levels of miR-142-3p are expressed and binding to EEEV’s 3’ UTR in microglia, which results degradation of the EEEV genome. We also expect to observe increased activation and proliferation in microglia infected with mutant EEEV or the
Alzheimer 's disease (AD) is a progressive degenerative disease of the brain from which there is no recovery. There are three brain abnormalities that are the hallmarks of the Alzheimer’s disease is initially caused by plaques buildup in the brain’s neurons as illustrated in figure 1. The support structure that allows the flow of the nutrients through the neurons gets damaged and ultimately there is loss of connection among the neurons and they die off (National Institute of Health, 2015). This causes the brain tissue to shrinks, which is called atrophies. All this ultimately lead the victim of this disease to face difficulties in governing emotions, recognize errors and patterns, coordinate movement, and remember. Ultimately, a person with AD loses all memory and mental functioning.
2010). The neuroinflammation is an early, non-specific immune reaction to tissue damage or pathogen invasion (Lee et al. 2010). Inflammation of the central nervous system (CNS) is characterized by increased glial activation, pro-inflammatory cytokine concentration, blood-brain-barrier permeability, and leukocyte invasion (Lee et al. 2010). Microglia are cells that support and protect neuronal functions (Lee at al. 2010). They act as the first and main form of active immune defense that orchestrate the endogenous immune response of the Central Nervous System. The microglia play a central role in the cellular response to pathological lesions such as Aβ. Aβ can attract and activate microglia, leading to clustering of microglia around Aβ deposits sites in the brain (Lee et al. 2010). Even though microglia have neuroprotective functions, neurotoxic mechanisms which involves continuous activation of microglia and toxic factors are released by microglia, which may lead to neuroinflammation (Lee et al. 2010). Astrocytes (star-shaped glial cells) are the most abundant cells in the brain and are located in the brain and spinal. Astrocytes have various functions such as: biochemical support of endothelial cells of the BBB, supplying nutrients to the nervous tissue, maintenance of extracellular ion balance, and healing the brain and spinal cord following traumatic injury (Lee et al., 2010). Chemokines are released by astrocytes which attract microglia and they further express proinflammatory products, thus increasing neuronal damage in the pathogenesis of AD (Lee et al., 2010). Astrocytes play a critical role in Aß clearance and degradation, and they also provide trophic support to neurons forming a protective barrier between Aß deposits and neurons (Wyss-Coray et al., 2003). Neurons contribute to the production of
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most widespread age-related neurodegenerative diseases. Both diseases impact a considerable number of people, where AD occurs in around 10 percent of the population greater than the age of 65 while PD occurs in roughly 1 percent of the population above the age of 65. AD is considered to be the most widespread cause of dementia, characterised by the progressive memory and cognitive deficits which impair ones day to day activities. The pathological hallmark of AD comprises of extracellular accumulation of senile plaques consisting of mainly amyloid-beta (Aβ) peptides, along with neurofibrillary tangles which are composed of the phosphorylated tau protein, located in the hippocampus and cortex. Conversely, PD is considered to be the most widespread movement disorder that is characterised by symptoms such as rigidity slow movements, resting tremor and other instabilities. The extreme loss of dopaminergic neurones in the substantia nigra is what defines PD, as the loss of this nerve cell can be linked to Lewy bodies containing aggregates of a soluble protein called α-synuclein.
Inflamed dopaminergic neurons release inflammatory mediators (IFNs, EGF, IL5, IL6, HGF, LIF and BMP2). Inflammatory mediators such TNFα, IL-1β, IL-6 are elevated in Parkinson’s disease , ,  . Early cytokine expression (via m-RNA stabilization) is then stimulated by binding of these inflammatory mediators toTLR4 receptor , . When released these cytokines induce activation of transcription factors such as Stat1 and Stat3 activation and Stat dimers in combination with NF-κB up regulate Jmjd3 expression . Inflammatory activation of microglia results due to activation of a transcriptional network by Stat1 and Stat3, in concert with Jmjd3. Proinflammatory cytokines are then released by activated microglia. These cytokines then cause activation of nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS). As a result of activation of these enzymes reactive oxygen species (ROS) and nitric oxide are formed , . Transcription factors such as NF-κB, STAT 1 and STAT 3 and SMAD7 are up regulated in the chronic, self sustaining environment of inflammation in the brain or neuroinflammation and causes microglial activation, which leads to Parkinson’s disease through autophagy of dopaminergic neurons and various other mechanisms which are largely unknown. However, autophagy is the leading
Alzheimer’s disease is a progressive decline in cognitive function. It affects the brain by damaging brain cells resulting in a decreased in cognitive function, physical mobility, swallowing and fine motor skills. This disease approximately 5.1 million Americans aged sixty-five or older (Alzheimer 's Association, 2015) of which approximately 700,000 will likely die this year (Alzheimer 's Association, 2015) of related symptoms such as aspiration pneumonia due to decreased swallowing ability. The progression of this disease is consistent and cannot be cured or slowed (Alzheimer 's Association, 2015). According to the Alzheimer’s Association, Alzheimer’s is one of the most expensive chronic disease in the United States estimating a cost of 226 billion dollars per year (Alzheimer 's Association, 2015). This debilitating disease is the sixth leading cause of death in the United States (Alzheimer 's Association, 2015).
Within the last century, and even merely in the past decade, incredible advancements in technology have allowed modern medicine to rapidly progress to extraordinary levels, leaving scientists with unprecedented understanding of the human body, and of the aging process especially. While the field of gerontology has flourished as a result and knowledge of physiological changes in the aging body increased, scientists still only have a some-what fundamental understanding of the normal aging brain, and even less of abnormal age-related changes in the brain.
Alzheimer 's disease which chronically leads to Senile Dementia, is a horrific change in homeostasis for human beings. The most obvious change in homeostasis from Alzheimer 's is loss of memory. Memory loss can vary from short term to long term. Alzheimer 's disease has been occurring in humans for a long time. This is a disease that affects different body systems, and interrupts homeostasis to a significant point. As Alzheimer 's disease is further investigated, there are more discoveries with how it is caused, what it affects, and how to reduce the risk of developing it. Alzheimer 's disease is a frightening disease that is represented in humans. There are many concerns with this disease that are worth finding out for the future victims
Alzheimer is a disorder in the brain, which causes the mind to forget some memories from person's past. Alzheimer was and still one of the largest problems that old people face in their life. Three main aspects in order to understand the term Alzheimer are the history of the term, the diagnosis, and its kinds.
Per the Alzheimer’s Association, Alzheimer’s is “a brain disease that causes a slow decline in memory, thinking and reasoning skills” (CA). It is the most common form of dementia, and accounts for over half of the recorded dementia cases (CA). What most people are unaware of is that there are three different severities to having Alzheimer’s (CB). Alzheimer's disease is a progressive, degenerative disorder that attacks the brain's nerve cells, resulting in loss of cognitive skills and behavioral changes (CE). Alzheimer's disease is the most common cause of dementia, or loss of intellectual function, among people aged 65 and older (CE). Alzheimer's disease is not a normal part of aging, despite how common it is among the population (CE).
Did you know “every 66 seconds an individual develops Alzheimer’s disease,” according to Bright Focus (Bright Focus). When divided out, that is about 1,309 people each day. Unfortunately, Alzheimer’s disease is only one of many dementia illnesses. Even still, Alzheimer’s is still the most common form. To truly understand Alzheimer’s disease one must comprehend what the disease is, the effects it has, and who is affected.
Alzheimer’s is a type of dementia that causes problems with memory, thinking, and behavior. The purpose of this paper is to discuss medical definition, etiology, signs and symptoms, stages of disease progression, risk factors, diagnosis, and treatment. Alzheimer’s disease is the most common cause of dementia. Alzheimer’s disease is Ultimately fatal.
Alzheimer’s is a disease that affect the brain and it is a form of dementia. It causes problems with cognition such as memory, thinking, visual perception and behavior. It is a progressive disease, in other words, it worsens over time. The exact cause of this disease is unknown, however, studies have shown that certain conditions may predispose a person to Alzheimer, such as smoking, depression, diabetes and midlife high blood pressure, to name a few (McCane, Huerther, 2015)
What is Alzheimer’s disease? How does it affect our lives? In today’s world, people may have a family member or simply a friend that has been diagnosed with Alzheimer’s disease. It is essential that people are educated about the definition, origin, effect, and treatment of Alzheimer’s disease because it is so much more than just memory loss.
A. This is a picture of my grandparents, they lived very happy and exciting lives. But, after their retirement something changed with my grandmother- she was unable to recognize the face of her husband, whom she had met when she was only 16 years old.