Other Neuroscience and Neurobiology Commons^™

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Complement Propagates Visual System Pathology After Traumatic Brain Injury, Davis Marchant Borucki

MUSC Theses and Dissertations

Background: Traumatic brain injury is associated with the development of visual system disorders, including deficits in visual acuity. Visual deficits can present with delay and worsen over time, suggesting that ongoing neuroinflammatory changes contribute to their development and progression. Complement activation is strongly associated with the neuroinflammatory response after TBI and has been shown to contribute to neuronal and synaptic loss. However, the contributions of complement activation after TBI to vision loss remains unclear.

Methods: We employed an open skull controlled cortical impact model of traumatic brain injury in adult male mice to study how TBI affects vision. Animals were …

Sex-Specific Effects Of Chaperone And Glial Defenses On Experimental Lewy Body Disease, Tarun Bhatia

Electronic Theses and Dissertations

Lewy body disorders are a group of neurodegenerative conditions characterized by the pathological misfolding and aggregation of the abundant protein, α-synuclein. The most common Lewy body disorders are Parkinson’s disease and dementia with Lewy bodies. Apart from ageing, male sex is a major risk factor for Lewy body disorders, as men are at ~1.5-fold higher risk for these diseases than women. Yet, preclinical studies on Lewy body disorders rarely examine sex as a biological variable, and the mechanisms underlying sex-skewedness in disease risk remain undetermined.

Here, we developed a sex-stratified model of Lewy body disorders by exposing primary neurons harvested …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

Rejuvenation Of The Epigenetic Landscape Of The Aged Brain Through Manipulation Of Circulating Factors, Edward Koellhoffer

Dissertations and Theses (Open Access)

The aging population of the United States is expanding at an alarming rate. The Center for Disease Control and Prevention estimates that the population of those age 65 years and older will reach over 50 million by 2020 and will double to 100 million by 2060. This will not only put a massive strain on national healthcare resources, but will also increase the number of those who are not able to live and function independently. It is becoming increasingly vital to understand how the brain changes with age and mechanisms to possibly protect and rejuvenate the aged brain to a …

Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh

Dissertations and Theses

No abstract provided.

Targeting Pro-Inflammatory Function Of Microglia Using Small Molecules To Combat Neurodegeneration, Gabrielle C. Williams, Priya Prakash, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Microglia are the brain’s resident immune cells that are responsible for maintaining homeostasis in healthy conditions. During injury or infection, resting microglia get activated and produce pro-inflammatory cytokines such as IL-1b, IL-1a, IL-6, etc. along with reactive oxygen species like nitric oxide (NO) to combat neuroinflammatory diseases such as Alzheimer’s disease (AD). Inflammation is characterized by the activation of resident-immune cells in the brain called microglia that respond to the eat-me signals released by the toxic amyloid beta peptides as well as the dying neurons in the microenvironment. Recent studies have shown that activated microglia induce neuronal death by secreting …

Differential Activation Of Microglia In An In Vitro Model Of Intracerebral Hemorrhage, Bhakti Patel

Renée Crown University Honors Thesis Projects - All

An in vitro model of intracerebral hemorrhage was established to examine the protective versus cytotoxic roles of microglia in the context of mild versus severe injury. Co-cultures of microglia, astrocytes, and granule neurons were prepared from the cerebellar cortex of neonatal rats, and grown in standard medium containing fetal bovine serum or, in some cases, a serum-free chemically defined medium. To mimic hemorrhagic stroke, co-cultures grown for 7-8 days in vitro were challenged with two different concentrations of the toxic blood product hemin, corresponding to a mild versus a severe brain bleed. Immunocyto-chemical, real-time RT-PCR, iron deposition, and cell survival …