The Participation of Microglia in Neurogenesis: A Review

Abstract

Adult neurogenesis was one of the most important discoveries of the last century, helping us to better understand brain function. Researchers recently discovered that microglia play an important role in this process. However, various questions remain concerning where, at what stage, and what types of microglia participate. In this review, we demonstrate that certain pools of microglia are determinant cells in different phases of the generation of new neurons. This sheds light on how cells cooperate in order to fine tune brain organization. It also provides us with a better understanding of distinct neuronal pathologies.

Keywords: adult neurogenesis; age; inflammation; microglia; neurodegenerative diseases.

Figure 1

Microglial subtypes. 1: Resting microglia with ramified morphology with a lot of processes and branches. miR-124 is involved in the resting state of microglia. 2: Activated microglia with ameboid morphology. 2a: M1, activated microglia associated with an inflammatory state. 2b: M2, microglia in an anti-inflammatory state. 3a: Cytokines that can produce an inflammatory environment, such as Il-6 or TNF-alpha. 3b: Cytokines with anti-inflammatory properties (Il-4, Il-10, for example).

Figure 2

Process of neurogenesis. 0: ANSC in a quiescent state. 1: Type 1 cell. ANSC-activated. 2: Type 2 cell (differentiating 2a and 2b because of their phenotype). TAPC. 3: Type 3 cell. Migratory neuroblast. 4: Immature neuron. 5: Mature neuron. A. Astrocyte. The yellow arrows represent the participation of microglia in this process: microglia are able to activate latent ANSCs by the CX3C chemokine receptor (CX3CR1) in the hippocampus of mice engaged in exercise. They also participate in neurogenesis, inducing apoptosis in some type 2 cells, before the microglia phagocytize them. In addition, newborn cells have to compete with mature neurons and microglia collaborate at this point because they phagocytize weak or less active synapses. Notch1 stimulates the quiescent state, preventing the excessive activation of ANSCs. Annexin V is able to reduce apoptosis and may increase the number of apoptotic TAPCs. Migratory neuroblasts differentiate into immature neurons, which are characterized by a transient expression of calretinin.