Stress increases peripheral axon growth and regeneration through glucocorticoid receptor-dependent transcriptional programs

Jessica K. Lerch; Jessica K. Alexander; Kathryn M. Madalena; Dario Motti; Tam Quach; Akhil Dhamija; Alicia Zha; John C. Gensel; Jeanette Webster Marketon; Vance P. Lemmon; John L. Bixby; Phillip G. Popovich

doi:10.1523/ENEURO.0246-17.2017

Stress increases peripheral axon growth and regeneration through glucocorticoid receptor-dependent transcriptional programs

Jessica K. Lerch, Jessica K. Alexander, Kathryn M. Madalena, Dario Motti, Tam Quach, Akhil Dhamija, Alicia Zha, John C. Gensel, Jeanette Webster Marketon, Vance P. Lemmon, John L. Bixby, Phillip G. Popovich

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32 Scopus citations

Abstract

Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity.

Original language	English
Article number	e0246-17.2017
Journal	eNeuro
Volume	4
Issue number	4
DOIs	https://doi.org/10.1523/ENEURO.0246-17.2017
State	Published - Jul 1 2017

Bibliographical note

Publisher Copyright:
© 2017 Lerch et al.

Funding

analyzed data; J.K.L., J.K.A., K.M.M., V.P.L., J.L.B., and P.G.P. wrote the paper. This work was supported by National Institute of Neurological Disorders and Stroke Grants R01 NS083942 (to P.G.P.) and R01 HD057632 (to V.P.L. and J.L.B.). *J.K.L. and J.K.A. contributed equally to this work. Acknowledgments: We thank Kate Zakharova and Perry Delvin for technical assistance. Correspondence should be addressed to either of the following: Jessica K. Lerch, 460 West 12th Avenue, BRT0696, Columbus, OH 43210, E-mail: [email protected]; or Phillip G. Popovich, 460 West 12th Avenue, BRT694, Columbus, OH 43210, E-mail: [email protected]. DOI:http://dx.doi.org/10.1523/ENEURO.0246-17.2017 Copyright © 2017 Lerch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Funders	Funder number
National Institute of Neurological Disorders and Stroke	R01 HD057632, R01NS083942

Keywords

Dorsal root ganglia
Glucocorticoid receptor
Plasticity
Stress

ASJC Scopus subject areas

General Neuroscience

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10.1523/ENEURO.0246-17.2017

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Lerch, J. K., Alexander, J. K., Madalena, K. M., Motti, D., Quach, T., Dhamija, A., Zha, A., Gensel, J. C., Marketon, J. W., Lemmon, V. P., Bixby, J. L., & Popovich, P. G. (2017). Stress increases peripheral axon growth and regeneration through glucocorticoid receptor-dependent transcriptional programs. eNeuro, 4(4), Article e0246-17.2017. https://doi.org/10.1523/ENEURO.0246-17.2017

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Stress increases peripheral axon growth and regeneration through glucocorticoid receptor-dependent transcriptional programs

Abstract

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Keywords

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