Abstract
Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for improvement of memory in Alzheimer's patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder caused by loss-of-function mutations in MECP2. The mechanism of DBS benefits has been elusive, however, so we assessed changes in gene expression, splice isoforms, DNA methylation, and proteome following acute forniceal DBS in wild-type mice and mice lacking Mecp2. We found that DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis and normalized expression of ~25% of the genes altered in Mecp2-null mice. Moreover, DBS induced expression of 17-24% of the genes downregulated in other intellectual disability mouse models and in post-mortem human brain tissue from patients with Major Depressive Disorder, suggesting forniceal DBS could benefit individuals with a variety of neuropsychiatric disorders.
Article and author information
Author details
Funding
National Institutes of Health (5R01NS057819)
- Huda Y Zoghbi
Howard Hughes Medical Institute (HHMI Investigator)
- Huda Y Zoghbi
Robert and Janice McNair Foundation (Student Scholar)
- Amy E Pohodich
Baylor Research Advocates for Student Scientists (Student Scholar)
- Amy E Pohodich
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All research and animal care procedures were approved by the Baylor College of Medicine Institutional Animal Care and Use Committee (approved protocols: AN-1013 and AN-5585). All surgery was performed under isofluorane anesthesia, and every effort was made to minimize pain and suffering.
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
Publication history
- Received: December 4, 2017
- Accepted: March 22, 2018
- Accepted Manuscript published: March 23, 2018 (version 1)
- Version of Record published: April 18, 2018 (version 2)
Copyright
© 2018, Pohodich et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,574
- Page views
-
- 488
- Downloads
-
- 18
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.