| First Author | Zhu LJ | Year | 2020 |
| Journal | CNS Neurosci Ther | Volume | 26 |
| Issue | 4 | Pages | 453-464 |
| PubMed ID | 31863649 | Mgi Jnum | J:325852 |
| Mgi Id | MGI:6874217 | Doi | 10.1111/cns.13269 |
| Citation | Zhu LJ, et al. (2020) Dentate nNOS accounts for stress-induced 5-HT1A receptor deficiency: Implication in anxiety behaviors. CNS Neurosci Ther 26(4):453-464 |
| abstractText | 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 (ONOO*) 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-ONOO*-5-HT1A receptor -nNOS) of stress-related anxiety. |
