Browsing by Author "Baker, Cassandra"
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Item Causality of Sex-Driven Dimorphism in a Relapsing-Remitting Murine Disease Model of Multiple Sclerosis(2017-10-12) Baker, CassandraMultiple sclerosis (MS) is the most common neurodegenerative autoimmune disorder that affects young adults. Autoimmune disorders display sexual dimorphic characteristics in disease susceptibility and progression to females over males. MS is characterized by the destruction of myelin sheaths that cover axons, disrupting neuronal activity and causing neurological deficits. Relapsing-Remitting Multiple Sclerosis (RRMS) is the most common progression of MS. RRMS disease progression begins with an acute onset of neuroinflammatory events followed by periods of remyelination followed by periods of demyelination. RRMS displays sexual dimorphic characteristics that favor females over males approaching a 4:1 ratio. Disruption of the blood brain barrier (BBB) allowing for leukocyte entry and chronic inflammation is considered the primary cause of MS pathogenesis. A disease-modifying molecule, sphingosine 1-phosphate receptor 2 (S1PR2), has shown to disrupt BBB integrity. This receptor has an increased expression in the female cerebellum, a disease susceptible region, compared to males. The underlying cause of the overproduction of S1PR2 has yet to be discovered.Treatment with an S1PR2 antagonist, JTE-013, has previously shown to lower clinical scores of disease severity in a commonly used murine model for MS, experimental autoimmune encephalomyelitis (EAE). Phenotypic analysis of inflammatory leukocyte infiltrates found in disease regions of the CNS is needed to further understand the effects of S1PR2 antagonism. This project was completed with contributions from Robyn Klein, Lauren Vollmer, Sindhu Manivasagam, and Jessica Williams from the Washington University at St. Louis, Infectious Diseases.Item Investigation of sex differences in microglial response to binge ethanol and exercise(Brain Sciences, 2017-10) Barton, Emily A.; Baker, Cassandra; Leasure, J. LeighThe female brain appears selectively vulnerable to the neurotoxic effects of alcohol, but the reasons for this are unclear. One possibility is an exaggerated neuroimmune response in the female brain, such that alcohol increases microglia number and reactivity to subsequent stimuli, such as exercise. It is important to better characterize the interactive neural effects of alcohol and exercise, as exercise is increasingly being used in the treatment of alcohol use disorders. The present study compared the number of microglia and evidence of their activation in alcohol-vulnerable regions of the brain (medial prefrontal cortex and hippocampus) in male and female rats following binge alcohol and/or exercise. Binge alcohol increased microglia number and morphological characteristics consistent with their activation in the female brain but not the male, regardless of exercise. Binge alcohol followed by exercise did increase the number of MHC II+ (immunocompetent) microglia in females, although the vast majority of microglia did not express MHC II. These results indicate that binge alcohol exerts sex-specific effects on microglia that may result in enhanced reactivity to a subsequent challenge and in part underlie the apparent selective vulnerability of the female brain to alcohol.