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A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output in male mice

  1. Charlotte Vanacker  Is a corresponding author
  2. Richard Anthony Defazio
  3. Charlene M Sykes
  4. Suzanne M Moenter  Is a corresponding author
  1. University of Michigan, United States
Research Article
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Cite this article as: eLife 2021;10:e68205 doi: 10.7554/eLife.68205

Abstract

GnRH neurons are the final central neural output regulating fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (KNDy neurons) are considered the main regulator of GnRH output. GnRH and KNDy neurons are surrounded by astrocytes, which can modulate neuronal activity and communicate over distances. Prostaglandin E2 (PGE2), synthesized primarily by astrocytes, increases GnRH neuron activity and downstream pituitary release of luteinizing hormone (LH). We hypothesized GFAP-expressing astrocytes play a role regulating GnRH and/or KNDy neuron activity and LH release. We used adenoassociated viruses to target designer receptor exclusively activated by designer drugs (DREADDs) to GFAP-expressing cells to activate Gq or Gi-mediated signaling. Activating Gq signaling in the preoptic area, near GnRH neurons, but not in the arcuate, increases LH release in vivo and GnRH firing in vitro via a mechanism in part dependent upon PGE2. These data suggest astrocytes can activate GnRH/LH release in a manner independent of KNDy neurons.

Data availability

Analysis code for calcium signals and event detection have been deposited to GitLab and are accessible at https://gitlab.com/um-mip/coding-project

Article and author information

Author details

  1. Charlotte Vanacker

    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United States
    For correspondence
    chmhv@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5289-9298
  2. Richard Anthony Defazio

    Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7302-7528
  3. Charlene M Sykes

    Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Suzanne M Moenter

    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United States
    For correspondence
    smoenter@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9812-0497

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37 HD034860)

  • Suzanne M Moenter

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 of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Michigan. The Institutional Animal Care and Use Committee at the University of Michigan approved all procedures (PRO00006816PRO00008797)

Reviewing Editor

  1. Joel K Elmquist, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: March 9, 2021
  2. Accepted: July 21, 2021
  3. Accepted Manuscript published: July 22, 2021 (version 1)

Copyright

© 2021, Vanacker 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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