1. Academic Validation
  2. Merazin hydrate produces rapid antidepressant effect by activating CaMKII to promote neuronal activities and proliferation in hippocampus

Merazin hydrate produces rapid antidepressant effect by activating CaMKII to promote neuronal activities and proliferation in hippocampus

  • Brain Res. 2023 Nov 2:148665. doi: 10.1016/j.brainres.2023.148665.
Ziwei Gao 1 Chao Lu 1 Yaping Zhu 1 Yuxin Liu 1 Yuesong Lin 2 Wenming Gao 2 Liyuan Tian 3 Lei Wu 4
Affiliations

Affiliations

  • 1 Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Department of Pharmacy, Nanjing 210029, China.
  • 2 Nanjing Luhe District Hospital of Traditional Chinese Medicine, Nanjing 211500, China.
  • 3 Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Department of Pharmacy, Nanjing 210029, China. Electronic address: tianliyuan2023@163.com.
  • 4 Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Department of Pharmacy, Nanjing 210029, China. Electronic address: xiaoleiyaoshi@163.com.
Abstract

In our previous studies, we demonstrated that merazin hydrate (MH) had rapid antidepressant effect, but the deep mechanism needed to be further investigated. In this study, we used depressive-like model, behavioral tests, Molecular Biology and pharmacological interventions to reveal the underlying mechanisms of MH's rapid antidepressants. We found that a single administration of MH was able to produce rapid antidepressant effects in chronic unpredictable mild stress (CUMS) exposed mice at 1 day later, similar to ketamine. Moreover, MH could not only significantly up-regulated the expressions of cFOS, but also obviously increased the number of Ki67 positive cells in hippocampal dentate gyrus (DG). Furthermore, we also found that the phosphorylated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) was significantly reduced by CUMS in hippocampus, which was also reversed by MH. In addition, pharmacological inhibition of CaMKII by using KN-93 (a CaMKII antagonist) blocked the MH's up-regulation of cFOS and Ki67 in hippocampal DG. To sum up, this study demonstrated that MH produced rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

Keywords

CaMKII; Hippocampus; Merazin hydrate; Neuronal activities; Proliferation; Rapid antidepressant.

Figures
Products
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    Product Name
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  • HY-15465
    99.19%, CaMK II 抑制剂‎