Neuronal nitric oxide synthase in dorsal raphe nucleus mediates PTSD-like behaviors induced by single-prolonged stress through inhibiting serotonergic neurons activity.
Biochem Biophys Res Commun
; 585: 139-145, 2021 12 31.
Article
em En
| MEDLINE
| ID: mdl-34801934
ABSTRACT
The pathogenesis of post-traumatic stress disorder (PTSD) remains largely unclear. A large body of evidence suggests that the abnormal level of serotonin (5-HT) is closely related to the onset of PTSD. Several reports reveal that nitric oxide (NO) affects extracellular 5-HT levels in various brain regions, but no consistent direction of change was found and the underlying mechanisms remain unknown. The most of serotonergic neurons in dorsal raphe nucleus (DRN), a major source of serotonergic input to the forebrain, co-expresses neuronal nitric oxide synthase (nNOS), a synthase derived nitric oxide (NO) in the central nervous system. Here, we found that the excessive expression of nNOS and thereby the high concentration of NO followed by single-prolonged stress (SPS) caused suppression of the activity of DRN 5-HT neurons, inducing PTSD-like phenotype including increased anxiety-like behaviors, enhanced contextual fear memory, and fear generalization. Our study uncovered an important role of DRN nNOS-NO pathway in the pathology of PTSD, which may contribute to new understanding of the molecular mechanism of PTSD.
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Base de dados:
MEDLINE
Assunto principal:
Transtornos de Estresse Pós-Traumáticos
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Estresse Psicológico
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Comportamento Animal
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Óxido Nítrico Sintase Tipo I
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Neurônios Serotoninérgicos
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Núcleo Dorsal da Rafe
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article