Microglia Involvement in Rett Syndrome

Rett syndrome is a devastating central nervous system (CNS) developmental disorder, which is caused in the majority of cases by mutation of the X-linked epigenetic factor methyl-CpG-binding protein (MeCP) 2. The disease, which affects primarily girls, features severe neurological sequelae, including seizures, stereotypies, impaired breathing, mental retardation, and locomotor deficits. A majority of patients also develop somatic symptoms including intestinal pathology, impaired growth, and osteopenia. Rett syndrome was long thought to be a disease solely involving neuronal dysfunction. However, we recently showed a prominent role for the immune cells, microglia, in the pathophysiology of the disease. In this chapter, we give a broad overview of Rett syndrome, and recent findings in microglial biology as they relate to CNS development and pathology. We further focus on microglia, the tissue-resident macrophages of the brain, as possible therapeutic targets in the amelioration of Rett syndrome.