1. Neuroscience
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Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity

  1. Amy E Pohodich
  2. Hari Yalamanchili
  3. Ayush T Raman
  4. Ying-Wooi Wan
  5. Michael Gundry
  6. Shuang Hao
  7. Haijing Jin
  8. Jianrong Tang
  9. Zhandong Liu
  10. Huda Y Zoghbi  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. Texas Children's Hospital, United States
Research Article
  • Cited 25
  • Views 2,776
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Cite this article as: eLife 2018;7:e34031 doi: 10.7554/eLife.34031

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.

Data availability

The following data sets were generated
    1. Pohodich AE
    2. Zoghbi HY
    (2018) RNA-Sequencing data - acute DBS
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE107357).
    1. Pohodich AE
    2. Zoghbi HY
    (2018) Whole-Genome bisulfite sequencing
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE107383).
    1. Pohodich AE
    2. Zoghbi HY
    (2018) RNA-Sequencing data - chronic DBS
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE111703).
The following previously published data sets were used

Article and author information

Author details

  1. Amy E Pohodich

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  2. Hari Yalamanchili

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  3. Ayush T Raman

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  4. Ying-Wooi Wan

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  5. Michael Gundry

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  6. Shuang Hao

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  7. Haijing Jin

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  8. Jianrong Tang

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  9. Zhandong Liu

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  10. Huda Y Zoghbi

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    For correspondence
    hzoghbi@bcm.edu
    Competing interests
    Huda Y Zoghbi, Senior editor, eLifeis one of the co-holders of U.S. Patent 6,709,817 Method of Screening Rett Syndrome by Detecting a Mutation in MECP2, March 23, 2004.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0700-3349

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

  1. Anne E West, Duke University School of Medicine, United States

Publication history

  1. Received: December 4, 2017
  2. Accepted: March 22, 2018
  3. Accepted Manuscript published: March 23, 2018 (version 1)
  4. 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.

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