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Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI

The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-t...

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Autores principales: Li, Gen, Bo, Binshi, Wang, Puxin, Qian, Peixing, Li, Mingzhe, Li, Yuyan, Tong, Chuanjun, Zhang, Kaiwei, Zhang, Baogui, Jiang, Tianzi, Liang, Zhifeng, Duan, Xiaojie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234627/
https://www.ncbi.nlm.nih.gov/pubmed/37261976
http://dx.doi.org/10.7554/eLife.84693
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author Li, Gen
Bo, Binshi
Wang, Puxin
Qian, Peixing
Li, Mingzhe
Li, Yuyan
Tong, Chuanjun
Zhang, Kaiwei
Zhang, Baogui
Jiang, Tianzi
Liang, Zhifeng
Duan, Xiaojie
author_facet Li, Gen
Bo, Binshi
Wang, Puxin
Qian, Peixing
Li, Mingzhe
Li, Yuyan
Tong, Chuanjun
Zhang, Kaiwei
Zhang, Baogui
Jiang, Tianzi
Liang, Zhifeng
Duan, Xiaojie
author_sort Li, Gen
collection PubMed
description The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.
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spelling pubmed-102346272023-06-02 Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI Li, Gen Bo, Binshi Wang, Puxin Qian, Peixing Li, Mingzhe Li, Yuyan Tong, Chuanjun Zhang, Kaiwei Zhang, Baogui Jiang, Tianzi Liang, Zhifeng Duan, Xiaojie eLife Medicine The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy. eLife Sciences Publications, Ltd 2023-06-01 /pmc/articles/PMC10234627/ /pubmed/37261976 http://dx.doi.org/10.7554/eLife.84693 Text en © 2023, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Li, Gen
Bo, Binshi
Wang, Puxin
Qian, Peixing
Li, Mingzhe
Li, Yuyan
Tong, Chuanjun
Zhang, Kaiwei
Zhang, Baogui
Jiang, Tianzi
Liang, Zhifeng
Duan, Xiaojie
Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI
title Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI
title_full Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI
title_fullStr Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI
title_full_unstemmed Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI
title_short Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI
title_sort instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional mri
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234627/
https://www.ncbi.nlm.nih.gov/pubmed/37261976
http://dx.doi.org/10.7554/eLife.84693
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