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The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus

The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying...

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Autores principales: Zhou, Hong, Zhu, Jiayu, Jia, Jie, Xiang, Wei, Peng, Hualing, Zhang, Yuejin, Liu, Bo, Mu, Yangling, Lu, Yisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755020/
https://www.ncbi.nlm.nih.gov/pubmed/36532368
http://dx.doi.org/10.1016/j.ynstr.2022.100492
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author Zhou, Hong
Zhu, Jiayu
Jia, Jie
Xiang, Wei
Peng, Hualing
Zhang, Yuejin
Liu, Bo
Mu, Yangling
Lu, Yisheng
author_facet Zhou, Hong
Zhu, Jiayu
Jia, Jie
Xiang, Wei
Peng, Hualing
Zhang, Yuejin
Liu, Bo
Mu, Yangling
Lu, Yisheng
author_sort Zhou, Hong
collection PubMed
description The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying mechanism of NAc-DBS in MDD treatment remains elusive. Using the chronic unpredictable mild stress (CUMS) mouse model, we found NAc-DBS rescued depression-like behaviors, and reversed high gamma oscillation reduction and neurogenesis impairment in the dorsal dentate gyrus. Inactivation of parvalbumin (PV)-positive interneurons (PVI) in the dorsal DG led to depression-like behavior and decreased adult neurogenesis. Further investigation elucidated the VTA-DG GABAergic projection and CA1-NAc projection might jointly participate in NAc-DBS therapeutic mechanism. Disinhibition of the VTA-DG GABAergic projection had an antidepressant effect, and inhibition of the CA1-NAc projection reduced the antidepressant effect of DBS-NAc. Moreover, disinhibiting the VTA-DG GABAergic projection or activating the CA1-NAc projection could increase PVI activity in the dorsal DG. These results showed PVI in the dorsal DG as an essential target in depression and NAc-DBS antidepressant mechanisms.
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spelling pubmed-97550202022-12-17 The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus Zhou, Hong Zhu, Jiayu Jia, Jie Xiang, Wei Peng, Hualing Zhang, Yuejin Liu, Bo Mu, Yangling Lu, Yisheng Neurobiol Stress Original Research Article The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying mechanism of NAc-DBS in MDD treatment remains elusive. Using the chronic unpredictable mild stress (CUMS) mouse model, we found NAc-DBS rescued depression-like behaviors, and reversed high gamma oscillation reduction and neurogenesis impairment in the dorsal dentate gyrus. Inactivation of parvalbumin (PV)-positive interneurons (PVI) in the dorsal DG led to depression-like behavior and decreased adult neurogenesis. Further investigation elucidated the VTA-DG GABAergic projection and CA1-NAc projection might jointly participate in NAc-DBS therapeutic mechanism. Disinhibition of the VTA-DG GABAergic projection had an antidepressant effect, and inhibition of the CA1-NAc projection reduced the antidepressant effect of DBS-NAc. Moreover, disinhibiting the VTA-DG GABAergic projection or activating the CA1-NAc projection could increase PVI activity in the dorsal DG. These results showed PVI in the dorsal DG as an essential target in depression and NAc-DBS antidepressant mechanisms. Elsevier 2022-09-22 /pmc/articles/PMC9755020/ /pubmed/36532368 http://dx.doi.org/10.1016/j.ynstr.2022.100492 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Zhou, Hong
Zhu, Jiayu
Jia, Jie
Xiang, Wei
Peng, Hualing
Zhang, Yuejin
Liu, Bo
Mu, Yangling
Lu, Yisheng
The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
title The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
title_full The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
title_fullStr The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
title_full_unstemmed The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
title_short The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
title_sort antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755020/
https://www.ncbi.nlm.nih.gov/pubmed/36532368
http://dx.doi.org/10.1016/j.ynstr.2022.100492
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