Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis
The effects of surveillant and inflammatory microglia on the adult hippocampal neurogenic cascade. During physiological conditions, surveillant microglia effectively phagocytose the excess of apoptotic newborn cells and may release antineurogenic factors such as TGF. This anti-inflammatory state is maintained by neuronal (tethered or released) fractalkine. Enriched environment drives microglia towards a phenotype supportive of neurogenesis, via the production of IGF-1. In contrast, inflammatory challenge triggered by LPS, irradiation, aging, or AD induces the production of proinflammatory cytokines such as IL-1, TNF, and IL-6 by microglia as well as resident astrocytes and infiltrating monocytes, neutrophils, and lymphocytes. These cytokines have profound detrimental effects on adult neurogenesis by reducing the proliferation, survival, integration, and differentiation of the newborn neurons and decreasing their recall during learning and memory paradigms.