Extensive clinical and experimental studies established that depression and mood disorders are highly prevalent neuropsychiatric conditions in Alzheimer's disease (AD). However, its neurochemical basis is not clearly understood. Thus, understanding the neural mechanisms involved in mediating the co-morbidity of depression and AD may be crucial in exploring new pharmacological treatments for this condition. The present study investigated the role of the agmatinergic system in β-amyloid (Aββ1-42) peptide-induced depression using forced swim test (FST) in mice. Following the 28th days of its administration, Aβ1-42 peptide produced depression-like behavior in mice as evidenced by increased immobility time in FST and increased expression of pro-inflammatory cytokines like IL-6 and TNF-α compared to the control animals. The Aβ1-42 peptide-induced depression and neuroinflammatory markers were significantly inhibited by agmatine -, moxonidine, 2-BFI and l-arginine by once-daily administration during day 8-27 of the protocol. The antidepressant-like effect of agmatine in Aβ1-42 peptide in mice was potentiated by imidazoline receptor I1 agonist, moxonidine and imidazoline receptor I2 agonist 2-BFI at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan and imidazoline receptor I2 antagonist, idazoxan Also, agmatine levels were significantly reduced in brain samples of β-amyloid injected mice as compared to the control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in β-amyloid induced a depressive-like behavior in mice. The data projects agmatine as a potential therapeutic target for the AD-associated depression and comorbidities.

中文翻译：

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胍丁胺改善阿尔茨海默病小鼠模型中抑郁样行为和海马神经炎症的表现。

广泛的临床和实验研究证实，抑郁症和情绪障碍是阿尔茨海默病 (AD) 中非常普遍的神经精神疾病。然而，其神经化学基础尚不清楚。因此，了解参与介导抑郁症和 AD 共病的神经机制可能对于探索这种疾病的新药理学治疗方法至关重要。本研究使用强迫游泳试验 (FST) 在小鼠中研究了胍丁胺能系统在 β-淀粉样蛋白 (Aββ1-42) 肽诱导的抑郁症中的作用。在给药第 28 天后，与对照动物相比，Aβ1-42 肽在小鼠中产生了类似抑郁的行为，这可以通过 FST 中的不动时间增加和促炎细胞因子（如 IL-6 和 TNF-α）的表达增加来证明。Aβ1-42 肽诱导的抑郁症和神经炎症标志物被丁胺、莫索尼定、2-BFI 和 l-精氨酸在协议的第 8-27 天每天一次给药显着抑制。咪唑啉受体 I1 激动剂、莫索尼定和咪唑啉受体 I2 激动剂 2-BFI 以亚有效剂量增强了胍丁胺在小鼠 Aβ1-42 肽中的抗抑郁作用。另一方面，它被咪唑啉受体 I1 拮抗剂依法沙坦和咪唑啉受体 I2 拮抗剂咪唑克生完全阻断。此外，与对照动物相比，注射 β-淀粉样蛋白的小鼠脑样本中的胍丁胺水平显着降低。综上所述，本研究表明内源性胍丁胺能系统和咪唑啉受体系统在 β-淀粉样蛋白诱导小鼠抑郁样行为中的重要性。数据将丁胺作为 AD 相关抑郁症和合并症的潜在治疗靶点。