Activation of LXRß Signaling in the Amygdala Confers Anxiolytic Effects Through Rebalancing Excitatory and Inhibitory Neurotransmission upon Acute Stress.
Neurotherapeutics
; 17(3): 1253-1270, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32297184
ABSTRACT
The balance of major excitatory (glutamate, Glu) and inhibitory (γ-aminobutyric acid, GABA), named as E/I neurotransmission, is critical for proper information processing. Anxiety-like responses upon stress are accompanied by abnormal alterations in the formation and function of synapses, resulting in the imbalance of E/I neurotransmission in the amygdala. Liver X receptors (LXRs), including LXRα and LXRß isoforms, are nuclear receptors responsible for regulating central nervous system (CNS) functions besides maintaining metabolic homeostasis. However, little is known about the contribution of LXRs in E/I balance in regulating anxiety-related behaviors induced by stress. In this study, we found stress-induced anxiety led to the expression reduction of LXRß not LXRα in mice amygdala. GW3965, a dual agonist for both LXRα and LXRß, alleviated anxiety-like behaviors of stressed mice through activation of LXRß, confirmed by the knockdown of LXRß mediated by lentiviral shRNAs in the basolateral amygdala (BLA). This was paralleled by correcting the disequilibrium of E/I neurotransmission in the stressed BLA. Importantly, GW3965 exerted anxiolytic effects by correcting the promoted amplitude and frequency of miniature excitatory postsynaptic current (mEPSC), and augmenting the decreased that of miniature inhibitory postsynaptic current (mIPSC) in the stressed BLA. This suggests that stress-induced anxiety-like behaviors can largely be ascribed to the deficit of LXRß signaling in E/I neurotransmission in BLA. These findings highlight the deficiency of LXRß signaling in the amygdala linked to anxiety disorder, and LXRß activation may represent a potential novel target for anxiety treatment with an alteration in synaptic transmission in the amygdala.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
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Ansiolíticos
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Potenciais Pós-Sinápticos Excitadores
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Potenciais Pós-Sinápticos Inibidores
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Receptores X do Fígado
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Tonsila do Cerebelo
Limite:
Animals
Idioma:
En
Revista:
Neurotherapeutics
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article