Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India; Government College of Pharmacy, Amravati, Maharashtra, 444 604, India.
Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India.
Neurotoxicology. 2020 Sep;80:1-11. doi: 10.1016/j.neuro.2020.06.002. Epub 2020 Jun 6.
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. The present study investigated the effect of chronic intra-hippocampal agmatine administration on β-Amyloid (Aβ) induced memory impairment in mice. Aβ peptide injected mice demonstrated impairment of cognitive abilities evaluated as reference memory error and working memory error in radial arm maze (RAM) and decreased exploration time for novel object as well as recognition index in novel object recognition (NOR) test along with elevation in Aβ peptide, β-Site APP cleaving enzyme 1 (BACE 1), microtubule-associated protein tau (MAPt), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and reduction in neprilysin and brain derived neurotrophic factor (BDNF) immunocontent within hippocampus and prefrontal cortex. Importantly, this was associated with a reduction in the agmatine levels following Aβ peptide administration. Chronic administration of agmatine from day 8-27, prevented the memory impairment in mice and normalized the neurochemical alteration within prefrontal cortex and hippocampus induced by Aβ peptide administration. However, it did not modulate the amyloid precursor protein and BACE expression. This study suggests that agmatine improves learning and memory impairment possibly through the down regulation of neuroinflammatory pathways in AD.
阿尔茨海默病（AD）是一种慢性进行性神经退行性疾病，其特征是细胞外β-淀粉样蛋白（Aβ）斑块的异常积累和神经元损伤。本研究探讨了慢性海马内胍丁胺给药对β-淀粉样蛋白（Aβ）诱导的小鼠记忆障碍的影响。Aβ肽注射小鼠在放射臂迷宫（RAM）中表现出认知能力受损，表现为参考记忆错误和工作记忆错误，并且在新物体识别（NOR）测试中对新物体的探索时间减少以及识别指数降低，同时Aβ肽、β-位 APP 裂解酶 1（BACE 1）、微管相关蛋白 tau（MAPt）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）升高，神经肽 Y 和脑源性神经营养因子（BDNF）免疫含量降低在海马体和前额叶皮层中。重要的是，这与 Aβ肽给药后胍丁胺水平降低有关。从第 8-27 天开始，慢性给予胍丁胺可预防小鼠的记忆障碍，并使 Aβ肽给药引起的前额叶皮层和海马神经化学改变正常化。然而，它并没有调节淀粉样前体蛋白和 BACE 的表达。这项研究表明，胍丁胺通过下调 AD 中的神经炎症途径来改善学习和记忆障碍。
