Dentate nNOS accounts for stress‐induced 5‐HT 1A receptor deficiency: Implication in anxiety behaviors
Autor: | Lei Chang, Xian-Hui Zhu, Qi-Gang Zhou, Yuan‐Yuan Li, Nan Sun, Meng-Ying Liu, Li-Juan Zhu, Yu‐Lin Tang, Jie Ren, Chu Xu, Guo‐liang Meng, Jing Zhang |
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Rok vydání: | 2020 |
Předmět: |
inorganic chemicals
0301 basic medicine medicine.medical_specialty Hippocampus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Internal medicine Medicine Pharmacology (medical) Chronic stress Receptor Cyclic guanosine monophosphate Pharmacology business.industry Dentate gyrus Psychiatry and Mental health 030104 developmental biology Endocrinology nervous system chemistry Knockout mouse cardiovascular system Anxiety 5-HT1A receptor medicine.symptom business 030217 neurology & neurosurgery |
Zdroj: | CNS Neuroscience & Therapeutics. 26:453-464 |
ISSN: | 1755-5949 1755-5930 |
Popis: | 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. |
Databáze: | OpenAIRE |
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