Cong Tan

Date of Graduation

2015

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Neurology

Committee Chair

James W Simpkins

Committee Co-Chair

Jason D Huber

Committee Member

James P O'Callaghan

Committee Member

Paola Pergami

Abstract

Microglia activation is associated with many neurodegenerative diseases such as Alzheimer's disease (AD). When activated, microglia cells change their morphology and become phagocytic. In the Alzheimer's brain, microglia cells play an important role in scavenging plaque-damaged cells and in clearing Abeta plagues. Soluble oligomeric Abeta (oAbeta) is capable to stimulate microglia activation. In AD brain, microglia cells accumulate around senile plaques as a hallmark of the pathology. Recently, we found that mitochondrial oxidative phosphorylation is affected in a dose-dependent manner in a microglia cell line (C8-B4) and primary rat glia cell. Mitochondrial basal, maximal and spare respiration capacities increase at low concentrations of oAbeta and then decline at higher concentrations. Flow cytometry for markers of microglial activation (IBA1 upregulation) similarly shows a low dose increase and a high dose decline. In contrast, the oAbeta stimulation does not alter the mitochondrial oxidative phosphorylation in a mouse hippocampal neuronal cell line (HT22), suggesting a brain cell-specific response to oAbeta. Our experiment results suggest that at low concentrations of oAbeta, which would normally occur in healthy brains, an increased mitochondrial respiration hints that microglia activation responds to mild oAbeta stimulation. In contract, at higher pathological levels of oAbeta, microglial activation and its associated mitochondrial functions are inhibited which may prevent phagocytosis and allow the accumulation of Abeta.

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