Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1
- University of Alabama at Birmingham, United States
- 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.
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Data from: BDNF/TrkB.T1 signaling is a novel mechanism for astrocyte morphological maturationNCBI Gene Expression Omnibus, GSE122176.
Article and author information
Author details
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.
Reviewing Editor
- Cagla Eroglu, Duke University, United States
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.
Version history
- Received: December 22, 2018
- Accepted: August 20, 2019
- Accepted Manuscript published: August 21, 2019 (version 1)
- Version of Record published: September 4, 2019 (version 2)
- 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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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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