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，抑郁和焦虑等情绪障碍在 II 型糖尿病 (T2DM) 中非常普遍。然而，T2DM 与抑郁症之间关系的神经生物学机制尚未确定。因此，了解介导抑郁症和 II 型糖尿病合并症的神经机制可能会为这种情况开启新的药物治疗。本研究使用强迫游泳试验 (FST) 和高架十字迷宫 (EPM) 大鼠中的焦虑，研究了胍丁胺能系统在 T2DM 诱导的抑郁症中的作用。T2DM 是由高脂肪饮食 (HFD) 和链脲佐菌素 (STZ) 注射液联合诱导的，并由高血糖水平证实。12 周后，喂食 HFD 和注射 STZ 的大鼠表现出抑郁样行为和焦虑。它与促炎细胞因子如 IL-6 和 TNF-α 的表达增加以及海马组织中 BDNF 免疫含量降低有关。T2DM 诱导的抑郁、焦虑和神经炎症标志物被丁胺 (10–20 mg/kg, ip) 显着抑制，在协议的第 9 至第 12 周期间每天给药一次。与正常喂养 (NF) 对照动物相比, T2DM 大鼠海马中的胍丁胺水平显着降低。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。该数据将丁胺作为 T2DM 相关抑郁症、焦虑症和合并症的潜在治疗靶点。并降低海马组织中的 BDNF 免疫含量。T2DM 诱发的抑郁、焦虑和神经炎症标志物被丁胺 (10–20 mg/kg, ip) 显着抑制，在协议的第 9 至第 12 周期间每天给药一次。与正常喂养 (NF) 对照动物相比, T2DM 大鼠海马中的胍丁胺水平显着降低。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。该数据将丁胺作为 T2DM 相关抑郁症、焦虑症和合并症的潜在治疗靶点。并降低海马组织中的 BDNF 免疫含量。T2DM 诱发的抑郁、焦虑和神经炎症标志物被丁胺 (10–20 mg/kg, ip) 显着抑制，在协议的第 9 至第 12 周期间每天给药一次。与正常喂养 (NF) 对照动物相比, T2DM 大鼠海马中的胍丁胺水平显着降低。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。该数据将丁胺作为 T2DM 相关抑郁症、焦虑症和合并症的潜在治疗靶点。在协议的第 9 至 12 周期间每天给药一次。与正常喂养 (NF) 对照动物相比, T2DM 大鼠海马中的胍丁胺水平显着降低。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。该数据将丁胺作为 T2DM 相关抑郁症、焦虑症和合并症的潜在治疗靶点。在协议的第 9 至 12 周期间每天给药一次。与正常喂养 (NF) 对照动物相比, T2DM 大鼠海马中的胍丁胺水平显着降低。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。该数据将丁胺作为 T2DM 相关抑郁症、焦虑症和合并症的潜在治疗靶点。