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Astrocyte Mediated Regulation of Activated Microglia: Implications for Exaggerated Microglial Activation in Aged Mice Following Peripheral Inflammatory Challenge

Year: 2015
Type: article
Abstract: Older individuals are at greater risk for infection and concomitant with this they have a higher frequency for developing neurobehavioral complications that negatively affect health and lifespan.For instance, otherwise innocuous infections are triggers for cognitive decline and the onset of depressive disorders in the elderly.This is a major issue because of the expansion of the elderly population.Neuroinflammation may be the key mechanism underlying the development of these neuropsychiatric disorders.Crosstalk between glial cells of the brain, including microglia and astrocytes, is normally involved in propagating inflammatory signals that are initiated in the periphery with infection.For example, microglia and astrocytes increased expression of inflammatory mediators following peripheral immune challenge in mice (Chapter 2).These increases in cytokine expression correlated to active sickness behavior in mice injected with the bacterial component lipopolysaccharide (LPS).Our work in aged mice, however, shows that aged microglia are hyperactive during an immune challenge and this results in prolonged neuroinflammation and the development of depression and cognitive impairments in the older mice.To limit inflammation, glial cells produce anti-inflammatory cytokines including interleukin (IL)-10.While IL-10 is also elevated in the aged brain following immune challenge, microglial activation still goes unresolved.Our studies show that there are dynamic interactions between microglia and astrocytes mediated by IL-10.For example, in adult mice astrocytes decrease pro-inflammatory activation following IL-This thesis is dedicated to Jason, we started OSBP together and we will finish together.To my parents, thank you for always believing in me, supporting me, and teaching me to set high goals.
Language: English
Subfield: Neurology
Open Access status: green
OpenAlex ID: W2888407793
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