Locus Coeruleus-Dorsolateral Septum Projections Modulate Depression-Like Behaviors via BDNF But Not Norepinephrine
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH..
Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression-like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH -dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression-like behaviors in both male and female mice. Mechanistically, it is found that brain-derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant-like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant-like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant-like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant-like role of the LCTH -dLSSST pathway in depression via BDNF-TrkB signaling.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 10 vom: 27. März, Seite e2303503 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Qian [VerfasserIn] |
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| Links: |
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| Themen: |
Antidepressive Agents |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202303503 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression-like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH -dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression-like behaviors in both male and female mice. Mechanistically, it is found that brain-derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant-like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant-like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant-like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant-like role of the LCTH -dLSSST pathway in depression via BDNF-TrkB signaling | ||
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| 700 | 1 | |a Wei, Ke |e verfasserin |4 aut | |
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| 700 | 1 | |a Ma, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Fangfang |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Gang |e verfasserin |4 aut | |
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