Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, M.S. 441 002, India.
Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, M.S. 441 002, India; Government College of Pharmacy, Amravati, M.S. 444 604, India.
Brain Res. 2020 Nov 15;1747:147045. doi: 10.1016/j.brainres.2020.147045. Epub 2020 Aug 3.
Epidemiological studies indicated that mood disorders like depression and anxiety are highly prevalent in type-II diabetes mellitus (T2DM). However, the neurobiological mechanisms underlying the relationship between T2DM and depression have yet to be identified. Thus, understanding the neural mechanisms that mediate the co-morbidity of depression and type-II diabetes mellitus may unlock new pharmacological treatments for this condition. The present study investigated the role of the agmatinergic system in T2DM induced depression using forced swim test (FST) and anxiety in the elevated plus-maze (EPM)in rats. T2DM was induced by the combination of high-fat diet (HFD) and streptozotocin (STZ) injection and confirmed by high blood glucose levels. After 12 weeks, HFD fed and STZ injected rats exhibited depression-like behaviors and anxiety. It was associated with increased expression of pro-inflammatory cytokines like IL-6 and TNF-α, and reduced BDNF immunocontent in the hippocampal tissues. The T2DM-induced depression, anxiety, and neuroinflammatory markers were significantly inhibited by agmatine (10-20 mg/kg, i.p.), by once-daily administration during 9th to 12th week of the protocol. Agmatine levels were significantly reduced in the hippocampus of T2DM rats as compared to the normal fed (NF) control animals. In conclusion, the present study suggests the importance of endogenous agmatine in T2DM induced anxiety and depressive-like behavior in rats. The data projects agmatine as a potential therapeutic target for T2DM-associated depression, anxiety, and comorbidities.
流行病学研究表明，抑郁症和焦虑症等情绪障碍在 2 型糖尿病（T2DM）中高发。然而，T2DM 与抑郁症之间的神经生物学机制尚未确定。因此，了解介导抑郁症和 2 型糖尿病共病的神经机制可能为这种疾病开辟新的药物治疗途径。本研究使用强迫游泳试验（FST）和高架十字迷宫（EPM）检测大鼠中的 T2DM 诱导的抑郁和焦虑，以研究胍丁胺系统的作用。T2DM 通过高脂肪饮食（HFD）和链脲佐菌素（STZ）注射联合诱导，并通过高血糖水平确认。12 周后，HFD 喂养和 STZ 注射大鼠表现出抑郁样行为和焦虑。这与海马组织中促炎细胞因子如 IL-6 和 TNF-α的表达增加以及 BDNF 免疫含量减少有关。胍丁胺（10-20mg/kg，腹腔注射）在方案的第 9 至 12 周期间每天一次给药，可显著抑制 T2DM 诱导的抑郁、焦虑和神经炎症标志物。与正常喂养（NF）对照动物相比，T2DM 大鼠海马中的胍丁胺水平明显降低。总之，本研究表明内源性胍丁胺在 T2DM 诱导的大鼠焦虑和抑郁样行为中的重要性。该数据表明胍丁胺可能是治疗与 T2DM 相关的抑郁、焦虑和共病的潜在治疗靶点。
