Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Apr;391(4):407-422. doi: 10.1007/s00210-018-1466-8. Epub 2018 Jan 29.
Several hypotheses link high fat diet (HFD) with the pathophysiology of depression and its response to antidepressants. This study aimed to determine the effect of metformin (MET) on the cognitive and antidepressant activity of fluoxetine (FLU) through its effect on c-Jun expression. Behavioral, cognitive function, biochemical, and histopathological studies were performed in non-HFD- and HFD-fed rats exposed to chronic restraint stress (CRS). Stressed group showed cognitive impairment, depressive-like symptoms, disturbed glucose homeostasis and lipid profile, reduced adiponectin level, brain-derived neurotrophic factor (BDNF) expression, and increased corticosterone and c-Jun. All these were aggravated by HFD. MET, FLU and their combination produced significant improvement in lipid profile with significant increase in adiponectin and BDNF expression. Corticosterone, body weight and insulin resistance showed significant decrease in the treated groups. Moreover, there was a significant decrease in hippocampal c Jun expression. There was a significant preferable effect toward the combination. Conclusion, MET may decrease the refractoriness to FLU and improves the cognition in individuals who are fed on HFD.
几种假说将高脂肪饮食（HFD）与抑郁症的病理生理学及其对抗抑郁药的反应联系起来。本研究旨在通过观察 c-Jun 表达，确定二甲双胍（MET）对氟西汀（FLU）的认知和抗抑郁活性的影响。在未接受 HFD 和接受 HFD 的大鼠中进行行为、认知功能、生化和组织病理学研究，使其暴露于慢性束缚应激（CRS）下。应激组表现出认知障碍、抑郁样症状、葡萄糖和脂质代谢紊乱、脂联素水平降低、脑源性神经营养因子（BDNF）表达减少，皮质酮和 c-Jun 增加。所有这些都因 HFD 而加重。MET、FLU 及其组合显著改善了血脂谱，显著增加了脂联素和 BDNF 的表达。皮质酮、体重和胰岛素抵抗在治疗组中显著降低。此外，海马体 c Jun 表达也显著降低。联合用药效果更为显著。结论，MET 可能降低 HFD 喂养个体对抗抑郁药 FLU 的耐药性，并改善认知功能。
