Role of Microglia in Modulating Adult Neurogenesis in Health and Neurodegeneration

Abstract

Microglia are the resident immune cells of the brain, constituting the powerhouse of brain innate immunity. They originate from hematopoietic precursors that infiltrate the developing brain during different stages of embryogenesis, acquiring a phenotype characterized by the presence of dense ramifications. Microglial cells play key roles in maintaining brain homeostasis and regulating brain immune responses. They continuously scan and sense the brain environment to detect any occurring changes. Upon detection of a signal related to physiological or pathological processes, the cells are activated and transform to an amoeboid-like phenotype, mounting adequate responses that range from phagocytosis to secretion of inflammatory and trophic factors. The overwhelming evidence suggests that microglia are crucially implicated in influencing neuronal proliferation and differentiation, as well as synaptic connections, and thereby cognitive and behavioral functions. Here, we review the role of microglia in adult neurogenesis under physiological conditions, and how this role is affected in neurodegenerative diseases.

Keywords: microglia; neurodegeneration; neurogenesis.

Figure 1

Microglia regulation of neurogenesis during lifespan: In the young healthy brain, microglia actively modulate neurogenesis via several supportive mechanisms that ensure the proper turnover of adult newly born neurons. A plethora of modulatory factors dictate microglial functions, and thereby influencing the rate of adult neurogenesis. Over age, microglia become less mobile, adopt an amoeboid-like phenotype, chronically express pro-inflammatory cytokines, and display an impaired phagocytic activity. The age-dependent establishment of a pro-inflammatory phenotype is accompanied by the release of neurotoxic cytokines, which impairs neurogenesis and synaptic integrity, and thereby contributing to neuronal loss and cognitive decline seen in Alzheimer’s disease (AD), and Parkinson’s disease (PD).