Deep Brain Stimulation and Repetitive Training Restore Neuronal Activity and Improve Neurological Function in Rett Syndrome Models.

Authors

Harini Pallikarana Tirumala, Yan Li, Huda Y Zoghbi

Published in

American journal on intellectual and developmental disabilities. Volume 131. Issue 4. Pages 294-303. Epub May 18, 2026.

Abstract

Rett syndrome (RTT) is a postnatal neurological disorder caused by loss-of-function mutations in the gene that encodes methyl-CpG binding protein 2. RTT is characterized by initially normal development, followed by developmental regression at 6 to 18 months of age. Individuals with RTT subsequently develop motor deficits, impaired learning and memory, and breathing abnormalities. In this review, we summarize recent findings on how neuronal circuitry is impaired in RTT and how deep brain stimulation and presymptomatic, task-specific training significantly improve learning and memory in RTT mice. Translating these findings to clinical applications, interventional studies have shown initial evidence that structured behavioral exercises can benefit individuals with RTT. Based on the converging evidence from preclinical and clinical research, we advocate for early-stage intensive behavioral training to supplement other therapeutic approaches and enhance treatment outcomes.

PMID:
42584873
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.

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