GABAergic Progenitor Cell Graft Rescues Cognitive Deficits in Fragile X Syndrome Mice.

Abstract

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons. MGE cell transplantation restores Ras-PKB signaling in pyramidal neurons, enhances AMPA receptor trafficking, rescues synaptic plasticity, and corrects abnormal hippocampal neural oscillations. These findings highlight the potential of GABAergic precursor cell transplantation as a promising therapeutic strategy for FXS.