The effects of microglia- and astrocyte-derived factors on neurogenesis in health and disease.

Hippocampal neurogenesis continues throughout life and has been suggested to play an essential role in maintaining spatial cognitive function under physiological conditions. An increasing amount of evidence has indicated that adult neurogenesis is tightly controlled by environmental conditions in the neurogenic niche, which consists of multiple types of cells including microglia and astrocytes. Microglia maintain the environment of neurogenic niche through their phagocytic capacity and interaction with neurons via fractalkine-CX3CR1 signaling. In addition, microglia release growth factors such as brain-derived neurotrophic factor (BDNF) and cytokines such as tumor necrosis factor (TNF)-α to support the development of adult born neurons. Astrocytes also manipulate neurogenesis by releasing various soluble factors including adenosine triphosphate and lactate. Whereas, under pathological conditions such as Alzheimer's disease, depression, and epilepsy, microglia and astrocytes play a leading role in inflammation and are involved in attenuating the normal process of neurogenesis. The modulation of glial functions on neurogenesis in these brain diseases are attracting attention as a new therapeutic target. This review describes how these glial cells play a role in adult hippocampal neurogenesis in both health and disease, especially focusing glia-derived factors.