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Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice

INTRODUCTION: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and is often accompanied by anxiety. In this study, we investigated whether the activation of VTA(Vgat) neurons could reduce anxiety in APP/PS1 mice. We hypothesized that acute soci...

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Autores principales: Yao, Di, Li, Rong, Kora, Musa, Huang, Hongqing, Liu, Xinghua, Gong, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076796/
https://www.ncbi.nlm.nih.gov/pubmed/37032820
http://dx.doi.org/10.3389/fnagi.2023.1142055
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author Yao, Di
Li, Rong
Kora, Musa
Huang, Hongqing
Liu, Xinghua
Gong, Song
author_facet Yao, Di
Li, Rong
Kora, Musa
Huang, Hongqing
Liu, Xinghua
Gong, Song
author_sort Yao, Di
collection PubMed
description INTRODUCTION: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and is often accompanied by anxiety. In this study, we investigated whether the activation of VTA(Vgat) neurons could reduce anxiety in APP/PS1 mice. We hypothesized that acute social defeat stress (SDS) would lead to anxiety in APP/PS1 mice, and that the activation of VTA(Vgat) neurons would alleviate this anxiety. METHODS: We exposed APP/PS1 mice to acute SDS and assessed anxiety using the open field test and elevated plus-arm test. Activated VTA(Vgat) neurons was tested by cfos staining. Sleep quality was detected using electroencephalogram after SDS or non-SDS procedure. Sleep duration, sleep latency, and non-rapid eye movement (NREM) percentage were analyzed. VTA(Vgat) neurons were chemogenetically activated by deschloroclozapine. RESULTS: Our results showed that acute SDS led to anxiety in APP/PS1 mice, as evidenced by increased anxiety-related behaviors in the open field and elevated plus-arm tests. Activation of VTA(Vgat) neurons by SDS led to an increase in sleep duration, primarily due to a decrease in sleep latency and an increase in NREMs. However, the quality of sleep was poor. Chemogenetical activation of VTA(Vgat) neurons improved sleep quality and relieved SDS-induced anxiety. Furthermore, the anxiety state correlated negatively with sleep duration and NREM percentage and correlated positively with theta power density in APP/PS1 mice. DISCUSSION: Our study provides evidence that the activation of VTA(Vgat) neurons alleviates SDS-induced anxiety in APP/PS1 mice, suggesting that poor sleep quality may exacerbate anxiety in AD. These findings may have important implications for the treatment of anxiety in AD, as targeting VTA(Vgat) neurons could be a potential therapeutic approach.
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spelling pubmed-100767962023-04-07 Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice Yao, Di Li, Rong Kora, Musa Huang, Hongqing Liu, Xinghua Gong, Song Front Aging Neurosci Aging Neuroscience INTRODUCTION: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and is often accompanied by anxiety. In this study, we investigated whether the activation of VTA(Vgat) neurons could reduce anxiety in APP/PS1 mice. We hypothesized that acute social defeat stress (SDS) would lead to anxiety in APP/PS1 mice, and that the activation of VTA(Vgat) neurons would alleviate this anxiety. METHODS: We exposed APP/PS1 mice to acute SDS and assessed anxiety using the open field test and elevated plus-arm test. Activated VTA(Vgat) neurons was tested by cfos staining. Sleep quality was detected using electroencephalogram after SDS or non-SDS procedure. Sleep duration, sleep latency, and non-rapid eye movement (NREM) percentage were analyzed. VTA(Vgat) neurons were chemogenetically activated by deschloroclozapine. RESULTS: Our results showed that acute SDS led to anxiety in APP/PS1 mice, as evidenced by increased anxiety-related behaviors in the open field and elevated plus-arm tests. Activation of VTA(Vgat) neurons by SDS led to an increase in sleep duration, primarily due to a decrease in sleep latency and an increase in NREMs. However, the quality of sleep was poor. Chemogenetical activation of VTA(Vgat) neurons improved sleep quality and relieved SDS-induced anxiety. Furthermore, the anxiety state correlated negatively with sleep duration and NREM percentage and correlated positively with theta power density in APP/PS1 mice. DISCUSSION: Our study provides evidence that the activation of VTA(Vgat) neurons alleviates SDS-induced anxiety in APP/PS1 mice, suggesting that poor sleep quality may exacerbate anxiety in AD. These findings may have important implications for the treatment of anxiety in AD, as targeting VTA(Vgat) neurons could be a potential therapeutic approach. Frontiers Media S.A. 2023-03-23 /pmc/articles/PMC10076796/ /pubmed/37032820 http://dx.doi.org/10.3389/fnagi.2023.1142055 Text en Copyright © 2023 Yao, Li, Kora, Huang, Liu and Gong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Yao, Di
Li, Rong
Kora, Musa
Huang, Hongqing
Liu, Xinghua
Gong, Song
Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
title Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
title_full Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
title_fullStr Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
title_full_unstemmed Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
title_short Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
title_sort activation of ventral tegmental area vesicular gaba transporter (vgat) neurons alleviates social defeat stress-induced anxiety in app/ps1 mice
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076796/
https://www.ncbi.nlm.nih.gov/pubmed/37032820
http://dx.doi.org/10.3389/fnagi.2023.1142055
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