Dentate nNOS accounts for stress-induced 5-HT1A receptor deficiency: Implication in anxiety behaviors.
CNS Neurosci Ther
; 26(4): 453-464, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-31863649
ABSTRACT
BACKGROUND:
Anxiety is a common disorder with high social burden worldwide. Dysfunction of serotonin-1A receptor (5-HT1A receptor) in the dentate gyrus (DG) of the hippocampus has been predominantly implicated in the anxiety behavior. However, the molecular mechanism underlying the deficiency of postsynaptic 5-HT1A receptor in regulating anxiety behavior remains unclear.METHODS:
Using pharmacological and genetic methods, we investigated the role of detate nNOS in 5-HT1A receptor decline and anxiety behavior induced by chronic mild stress (CMS) in mice.RESULTS:
Here we showed that local elevation of glucocorticoids in the DG accounted for chronic stress-induced anxiety behavior. Neuronal nitric oxide synthase (nNOS) mediated chronic stress-induced downregulation of 5-HT1A receptor in the DG through peroxynitrite anion (ONOOâ¢) pathway but not cyclic guanosine monophosphate (cGMP) pathway. By using pharmacological tool drugs and nNOS knockout mice, we found that nNOS in the DG played a key role in chronic stress-induced anxiety behavior.CONCLUSIONS:
These findings uncovered an important role of nNOS-5-HT1A receptor pathway in the DG of the hippocampus in chronic stress-induced anxiety. Accordingly, we developed a "dentate nNOS-5-HT1A receptor closed-loop" theory (stress-glucocorticoids-nNOS-Nitric oxide-ONOOâ¢-5-HT1A receptor -nNOS) of stress-related anxiety.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ansiedad
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Estrés Psicológico
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Giro Dentado
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Receptor de Serotonina 5-HT1A
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Óxido Nítrico Sintasa de Tipo I
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article