KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome
Abstract
Rett syndrome is a devastating neurodevelopmental disorder that currently has no cure. In this work, we demonstrate that human neurons derived from patients with Rett syndrome show a significant deficit in neuron-specific K + -Cl − cotransporter2 (KCC2) expression, resulting in a delayed GABA functional switch. Restoring KCC2 level rescues GABA functional deficits in Rett neurons. We further demonstrate that methyl CpG binding protein 2 regulates KCC2 expression through inhibiting RE1-silencing transcriptional factor. Our data suggest a potential therapeutic approach for the treatment of Rett syndrome through modulation of KCC2.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 05, 2016
- Source ID
- 10.1073/pnas.1524013113
Entities
People
- Alysson R. Muotri
- Cassiano Carromeu
- Eric Wengert
- Fred H. Gage
- Gong Chen
- Julie Kim
- Lei Zhang
- Li Zhou
- Maria C. N. Marchetto
- Xin Tang
- Zheng Wu
Organizations
- Brain & Behavior Research Foundation
- Bucknell University
- California Institute for Regenerative Medicine
- Leona M. and Harry B. Helmsley Charitable Trust
- National Institute of Mental Health
- National Institutes of Health
- Office of the Director
- Pennsylvania State University
- Salk Institute for Biological Studies
- United States Department of Defense
- University of California, San Diego