Satellite glia modulate sympathetic neuron survival, activity, and autonomic function
Abstract
Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, the extent to which sympathetic functions are influenced by satellite glia in vivo remains unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via K+-dependent mechanisms. These findings highlight neuron-satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.
Data availability
All data generated or analysed during this study are included in the manuscript (Results, Materials and Methods, and Figure Legends).
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Author details
Funding
National Institutes of Health (NS073751)
- Rejji Kuruvilla
National Institutes of Health (NS107342)
- Rejji Kuruvilla
National Science Foundation (DGE-1746891)
- Aurelia A Mapps
National Institutes of Health (DC016065)
- Haiqing Zhao
National Institutes of Health (EY027202)
- Haiqing Zhao
National Institutes of Health (ZIAMH002964)
- Samer Hattar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Moses V Chao, New York University Langone Medical Center, United States
Ethics
Animal experimentation: All procedures relating to animal care and treatment conformed to The Johns Hopkins University Animal Care and Use Committee (ACUC, protocol#MO19A488) and NIH guidelines.
Version history
- Preprint posted: September 23, 2021 (view preprint)
- Received: September 28, 2021
- Accepted: August 22, 2022
- Accepted Manuscript published: August 23, 2022 (version 1)
- Accepted Manuscript updated: August 25, 2022 (version 2)
- Version of Record published: August 31, 2022 (version 3)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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