Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

  1. Leanne M Holt
  2. Raymundo D Hernandez
  3. Natasha L Pacheco
  4. Beatriz Torres Ceja
  5. Muhannah Hossain
  6. Michelle Olsen  Is a corresponding author
  1. University of Alabama at Birmingham, United States
  2. Virginia Polytechnic Institute and State University, United States

Abstract

Brain derived neurotrophic factor (BDNF) is a critical growth factor involved in the maturation of the CNS, including neuronal morphology and synapse refinement. Herein, we demonstrate astrocytes express high levels of BDNF's receptor, TrkB (in the top 20 of protein-coding transcripts), with nearly exclusive expression of the truncated isoform, TrkB.T1, which peaks in expression during astrocyte morphological maturation. Using a novel culture paradigm, we show that astrocyte morphological complexity is increased in the presence of BDNF and is dependent upon BDNF/TrkB.T1 signaling. Deletion of TrkB.T1, globally and astrocyte-specifically, in mice revealed morphologically immature astrocytes with significantly reduced volume, as well as dysregulated expression of perisynaptic genes associated with mature astrocyte function. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis or function. These data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphological maturation, a critical process for CNS development.

Data availability

Sequencing data have been deposited in GEO under accession code GSE122176.

The following data sets were generated

Article and author information

Author details

  1. Leanne M Holt

    Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Raymundo D Hernandez

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Natasha L Pacheco

    Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9617-8887
  4. Beatriz Torres Ceja

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Muhannah Hossain

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michelle Olsen

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    For correspondence
    molsen1@vt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1394-664X

Funding

National Institute of Neurological Disorders and Stroke (F31NS100259)

  • Leanne M Holt

National Institute of Neurological Disorders and Stroke (R01NS075062)

  • Michelle Olsen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed according to NIH guidelines and with approval from the Animal Care and Use Committee of the University of Alabama at Birmingham (#20650) and Virginia Polytechnic Institute and State University (#17-012). Every effort was made to minimize pain and discomfort.

Reviewing Editor

  1. Cagla Eroglu, Duke University, United States

Publication history

  1. Received: December 22, 2018
  2. Accepted: August 20, 2019
  3. Accepted Manuscript published: August 21, 2019 (version 1)
  4. Version of Record published: September 4, 2019 (version 2)
  5. Version of Record updated: March 19, 2021 (version 3)

Copyright

© 2019, Holt 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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  1. Leanne M Holt
  2. Raymundo D Hernandez
  3. Natasha L Pacheco
  4. Beatriz Torres Ceja
  5. Muhannah Hossain
  6. Michelle Olsen
(2019)
Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1
eLife 8:e44667.
https://doi.org/10.7554/eLife.44667

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