Details

Autor(en) / Beteiligte

• Sun, Nan
• You, Yue
• Yang, Di
• Jiang, Zhi-Xin
• Xia, Tian
• Zhou, Qi-Gang
• Zhu, Dong-Ya

Titel

Neuronal nitric oxide synthase in dorsal raphe nucleus mediates PTSD-like behaviors induced by single-prolonged stress through inhibiting serotonergic neurons activity

Ist Teil von

• Biochemical and biophysical research communications, 2021-12, Vol.585, p.139-145

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. •Single-prolonged stress caused abnormal overexpression of nNOS in the DRN.•Conditional knockout of nNOS in DRN rescued SPS induced PTSD-like behaviors.•nNOS-derived NO in DRN contributed to the PTSD-like behaviors induced by SPS.•Excessive NO in the DRN after SPS exposure inhibits 5-HT neurons activity.