一种新的二肽H-MGL可部分改善stz诱导的老年痴呆模型雄性大鼠的记忆损伤

Sarieh Ghasempour, N. Maghsoudi, H. Manaheji, Rasoul Ghasemi, Ali Jaafari Suha, J. Zaringhalam
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摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是记忆和认知功能逐渐下降。根据Aβ斑块的沉积、细胞内神经原纤维缠结的积聚和神经元的损失来分类。神经营养因子在阿尔茨海默病的治疗中起关键作用。然而,这些神经营养因子的利用遇到了一定的困难和副作用。新的技术进步优先创新二肽的使用,提供更少的副作用。本研究旨在分析新发现的神经营养因子类二肽化合物六亚甲二胺双-(n -单琥珀酰-谷氨酰基-lysine)(实验室名称:H-MGL)对单剂量链脲佐剂(STZ)诱导的大鼠老年痴呆模型的记忆损伤作用。我们将STZ组和STZ+H-MGL组(1和2mg/kg)分为4组。STZ注射后连续给予H-MGL 14 d,进行Morris水迷宫试验。结果表明,STZ可显著增加小鼠的平均逃避潜伏期和平均行走距离。与STZ相比,1mg/kg剂量的H-MGL对大鼠没有明显的改善作用。2mg/kg H-MGL可显著降低小鼠第一次穿越平台的潜伏期和穿越平台的频率。因此,上述发现产生了H-MGL部分改善认知障碍的概念,因此它可能有希望以低副作用减轻阿尔茨海默病的认知缺陷,或潜在地减少与其进展相关的症状。
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A New Dipeptide H-MGL Partially Ameliorates Memory Impairment in an STZ-Induced Alzheimer Model in Male Rats
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is identified by the gradual decline in memory and cognitive function. It is classified by the deposition of Aβ plaques, the build-up of intracellular neurofibrillary tangle and neuron loss. Neurotrophic factors play critical role in the treatment of Alzheimer's disease. However, the utilization of such neurotrophins has encountered certain difficulties and side effects. Novel technological advancements prioritize innovative dipeptides usage, which offer fewer side effects. The present study endeavors to analyze the compound hexamethylenediamide bis-(N-monosuccinyl-glutamyl-lysine) (Lab name: H-MGL), a newly discovered neurotrophin mimetic dipeptide, with the aim of alleviating memory impairment in an intracerebroventricular single dose streptozotocin (STZ)-induced Alzheimer model in rats. We arranged 4 groups consist of sham, groups receiving STZ and STZ+H-MGL (1 and 2mg/kg). The H-MGL was administered consecutively for 14 days following STZ injection subsequently, the Morris Water Maze test was performed. The findings suggest that administration of STZ caused significantly increment in mean escape latency and mean traveled distance in acquisition days. H-MGL at a dosage of 1mg/kg failed to yield any notable improvement in rats when compared to STZ. By contrast, a dosage of 2mg/kg of H-MGL led to a significant decrease in the latency to first platform crossing and frequency of platform crossings. Consequently, the aforementioned findings have engendered the notion that H-MGL partially ameliorate cognitive impairment so it may hold promise for having low side effects to alleviate cognitive deficits in Alzheimer's disease, or potentially decreases the symptoms associated with its progression.
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