Excitation and Inhibition Imbalance in Rett Syndrome

• Published in: Frontiers in neuroscience Vol. 16; p. 825063
• Main Author: Li, Wei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 18.02.2022; Frontiers Media S.A
• Subjects: Autism; Brain research; Convulsions & seizures; Coordination; excitation/inhibition balance; Hyperactivity; MeCP2; MeCP2 protein; Methyl-CpG binding protein; Mutation; neurodevelopmental disorder; Neurodevelopmental disorders; Neuroscience; Pathogenesis; Rett syndrome; Rodents; Seizures; synaptic transmission; MeCP2; synaptic transmission; excitation/inhibition balance; neurodevelopmental disorder; Rett syndrome
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2022.825063

A loss of the excitation/inhibition (E/I) balance in the neural circuit has emerged as a common neuropathological feature in many neurodevelopmental disorders. Rett syndrome (RTT), a prevalent neurodevelopmental disorder that affects 1:10,000–15,000 women globally, is caused by loss-of-function mutations in the Methyl-CpG-binding Protein-2 ( Mecp2 ) gene. E/I imbalance is recognized as the leading cellular and synaptic hallmark that is fundamental to diverse RTT neurological symptoms, including stereotypic hand movements, impaired motor coordination, breathing irregularities, seizures, and learning/memory dysfunctions. E/I balance in RTT is not homogeneously altered but demonstrates brain region and cell type specificity instead. In this review, I elaborate on the current understanding of the loss of E/I balance in a range of brain areas at molecular and cellular levels. I further describe how the underlying cellular mechanisms contribute to the disturbance of the proper E/I ratio. Last, I discuss current pharmacologic innervations for RTT and their role in modifying the E/I balance.