Microglia, the brain-resident macrophages of haematopoietic origin, is involved in the pathology of many neurological disorders. Microglia from mouse model of the X-linked autism spectrum disorder Rett syndrome (RTT), have been shown to cause excitotoxicity through release of abnormally high levels of glutamate. One recent study showed that transplantation of wild-type bone marrow or targeted expression of MeCP2 in myeloid attenuated the symptoms of RTT in the mouse models, indicating that wild-type MeCP2-expressing microglia within the context of RTT can arrest the disease pathology. This study thus implicates microglia as a major player in RTT, and may open up a new avenue for treatment of this autism spectrum disorder.
Rett syndrome (RTT), typically caused by mutations in the X-linked MECP2 encoding Methyl-CpG-binding protein 2 (MeCP2), is a neurodevelopmental disorder that mainly affects females. RTT patients develop normally until 6–18 months of age but then show progressive loss of spoken language, loss of hand use, and the development of distinctive hand stereotypes. Clinical features include deceleration of brain growth, cognitive and motor abnormalities, autism, seizures, and respiratory dysfunction. MeCP2 is a DNA-binding protein that can both activate and repress transcription. MeCP2 also affects differential splicing. Investigating the biological targets of MeCP2 may help elucidate the mechanisms underlying RTT.