Rapid and Prolonged Antidepressant-like Effect of Crocin Is Associated with GHSR-Mediated Hippocampal Plasticity-related Proteins in Mice Exposed to Prenatal Stress
| Autor: | Dong Xiao, Ruyan Wu, Weiwei Tao, Yu Dong, Xin Shan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Physiology
Offspring Cognitive Neuroscience Growth hormone secretagogue receptor Hippocampal formation Pharmacology Hippocampus Biochemistry Crocin Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Medicine Receptors Ghrelin Adverse effect PI3K/AKT/mTOR pathway 030304 developmental biology Mice Inbred BALB C 0303 health sciences Neuronal Plasticity business.industry digestive oral and skin physiology Cell Biology General Medicine Carotenoids Antidepressive Agents chemistry Prenatal stress Antidepressant Female business Stress Psychological 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | ACS Chemical Neuroscience. 11:1159-1170 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.0c00022 |
| Popis: | Prenatal stress (PNS) has a prolonged and adverse effect on offspring, leading to a significantly increased vulnerability to developing depression in their later life. Traditional therapies have delayed onset and limited efficacy; thus, it remains an urgent need to find novel medications with fast-onset and high-efficacy potentials. Crocin, with its structure clearly examined, has shown antidepressant-like effects. However, few studies extensively investigated its effect especially in mice exposed to PNS. Using an established PNS model, we tested whether crocin could have a rapid and persistent antidepressant-like effect in PNS mice. Growth hormone secretagogue receptor (GHSR) and phosphoinositide 3-kinase (PI3K) inhibitors were used to test their effects in antidepressant-like effect of crocin. Hippocampal GHSR-PI3K signaling was examined both in PNS mice treated with a single dose of crocin and in combination of GHSR inhibitor. PNS mice showed depression-like behaviors at juvenile and adulthood, and crocin induced an instant and persistent antidepressant-like response in PNS mice in a dose-dependent manner. Moreover, crocin increased the expression of hippocampal synaptic plasticity-associated proteins through the restoration of GHSR-PI3K signaling. Inhibitions of both GHSR and PI3K abolished the effect of crocin in alleviating depressive-like behaviors. More importantly, GHSR inhibitor JMV2959 blocked the enhanced expression of hippocampal plasticity-related proteins induced by crocin. The present study demonstrated that crocin induced a fast-onset and prolonged antidepressant effect in PNS mice and suggested that GHSR-PI3K signaling may play a key role in crocin's effect at least partially by a restoration of hippocampal synaptic plasticity-associated proteins. |
| Databáze: | OpenAIRE |
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