Possible involvement of endogenous DNA-induced microglial activation in the pathogenesis of Rett syndrome

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder caused by methyl-CpG binding protein 2 (MECP2) mutations and accumulating evidence suggest that dysfunction of non-neuronal cells also participates in the RTT. We here report that the number of activated microglia is increased in the hippocampus of MeCP2 knock-out (KO) mice. This activation was suppressed in DNA recognizing Toll-like receptor 9 (TLR9) gene heterozygous MeCP2KO mice associated with attenuation of RTT phenotype observed in MeCP2KO mice. Thus, endogenous DNA may pertain to the RTT pathogenesis through microglial activation.