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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Ghrelin produces antidepressant-like effect in the estrogen deficient mice
Jie Fan1, Bing Jin Li1, Xue Feng Wang1
1Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Abstract:
Recent evidence shows that ghrelin plays an important role in depression. However, it was little known whether ghrelin produces antidepressant-like effect in the ovariectomized mice. The present study was aimed to investigate the antidepressant-like effects of the ghrelin in ovariectomized mice. In the forced swim test, ghrelin significantly decreased immobility time, reversing the "depressive-like" effect observed in ovariectomized mice, and this effect was reversed by the tamoxifen. In addition, immunohistochemical study indicated that ghrelin treatment reversed the reductions in c-Fos expression induced by ovariectomy. An estrogen antagonist tamoxifen also antagonized the effect of ghrelin on the c-Fos expression. Furthermore, the western blotting indicated that brain-derived neurotrophic factor (BDNF) in the hippocampus, but not phosphorylated cAMP response element-binding protein (pCREB)/CREB in the frontal cortex, were affected by ghrelin treatment. Ghrelin treatment significantly increased BrdU expression. Therefore, these findings suggest that ghrelin produces antidepressant-like effects in ovariectomized mice, and estrogen receptor may be involved in the antidepressant-like effects of the ghrelin.
Insights
Ghrelin demonstrates antidepressant-like effects in ovariectomized mice by reducing immobility and increasing brain-derived neurotrophic factor (BDNF). Estrogen receptors appear to mediate these beneficial impacts, suggesting a novel therapeutic avenue.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Ghrelin, a hormone, is increasingly recognized for its role in mood regulation and depression.
- The specific antidepressant-like effects of ghrelin in the context of ovariectomized mice, a model for postmenopausal depression, remain largely unexplored.
Purpose of the Study:
- To investigate the potential antidepressant-like effects of ghrelin administration in ovariectomized mice.
- To elucidate the underlying mechanisms, including the involvement of estrogen receptors and key neurotrophic factors.
Main Methods:
- Ovariectomized mice were treated with ghrelin, and their behavior was assessed using the forced swim test.
- Immunohistochemistry was employed to evaluate c-Fos expression, while western blotting analyzed brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB)/CREB levels.
- Bromodeoxyuridine (BrdU) expression was measured to assess cell proliferation.
Main Results:
- Ghrelin significantly reduced immobility time in the forced swim test, indicating antidepressant-like activity.
- Tamoxifen, an estrogen antagonist, reversed the effects of ghrelin on immobility and c-Fos expression.
- Ghrelin treatment increased hippocampal BDNF levels and BrdU expression, suggesting neuroprotective and neurogenic effects.
Conclusions:
- Ghrelin exhibits significant antidepressant-like effects in ovariectomized mice.
- The involvement of estrogen receptors is implicated in mediating ghrelin's antidepressant actions.
- Ghrelin may represent a potential therapeutic agent for depression, particularly in conditions associated with estrogen deficiency.
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