The Research Of The Pro-neurogenic Effect Of The Alternative Activation Of Microglia Involving With BDNF Signaling Pathway

Neurogenesis in the brain of adult mammals occurs throughout life, and has been clearly demonstrated at two locations under normal conditions: the subventricular zone(SVZ) of the lateral ventricles and the subgranular zone(SGZ) of the dentate gyrus in the hippocampus. These cells may be required for certain forms of brain function involving the olfactory bulb and the hippocampus, which is important for some forms of learning and memory. Microglia are the principal immune effector cells in the CNS, and play an essential role in shaping adult hippocampal neurogenesis. Microglia may exert both detrimental and beneficial effects on adulthood neurogenesis depending on their morphological and molecular phenotype. The classic activated microglia(M1) display pro-inflammatory phenotype, and have negative effects on neurogenesis. In contrast, the alternative activated microglia(M2) show increased expression of anti-inflammatory cytokines and nerve growth factors, and play a supportive role in regenerative processes. Brain-derived neurotrophic growth factor(BDNF) is one of the key factor involved in neurogenesis through the BDNF-TrkB interaction. It is hypothesized that the pro-neurogenic activity of M2 microglia involving with BDNF signaling pathway. The microglia were stimulated in vitro for 24 h either by IFN-γ(100ng/ml) or IL-4(10ng/ml) to induce M1 or M2 phenotype. With the co-culture of neural progenitor cells(NPCs) and,microglia, the neurogenesis was enhanced by of IL-4-stimulated(M2) microglia and arrested by IFN-γ-stimulated(M1) microglia. It was found that IL-4-stimulated microglia have a higher expression of BDNF than IFN-γ-stimulated microglia. The pro-neurogenic activity of M2 was blocked by anti-BDNF antibody or by K252 a, a selective inhibitor of TrkB.These results suggest that the alternative activation of microglia have a pro-neurogenic effect, which is involved with the BDNF signaling pathway.