期刊
ACS CHEMICAL NEUROSCIENCE
卷 11, 期 16, 页码 2472-2481出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.0c00246
关键词
Merazin hydrate; lipopolysaccharide; nitric oxide; NF-kappa B; CREB; BDNF
资金
- National Natural Science Foundation of China [81573797, 81872967]
- Jiangsu Province's colleges and universities (integration of Chinese and Western medicine)
- Nanjing University of Chinese Medicine focused on high-level talent training projects
Merazin hydrate (MH), an essential ingredient of Fructus aurantii, has been identified to have an antidepressant-like effect. However, the molecular mechanisms of MH modulate depressive behavior are largely uncharacterized. Here, in lip-opolysaccharide-induced mice, we identified that a single administration of MH recovered depressive behaviors and down-regulated the expressions of neuronal nitric oxide synthase (nNOS) in the hippocampus after 1 day. Activation of nNOS by L-arginine led to depressive behaviors, and inhibition of nNOS contributed to antidepressive behaviors. Notably, MH only reversed the expression of nNOS's downstream NF-kappa B and not the CREB/BDNF pathway in the hippocampus, and MH's antidepressant-like effects were prevented by Asatone (an agonist of NF-kappa B) and not H89 (an antagonist of CREB). MH also normalized the expressions of GFAP and IB-1 in dentate gyrus in the hippocampus and inflammatory factors such as IL-1 beta, IL-10, and TNF-alpha in serum. Overall, our studies reveal the molecular mechanisms of MH's antidepressant-like effect.
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