Ghasempour Sarieh, Maghsoudi Nader, Manaheji Homa, Ghasemi Rasoul, Jaafarisuha Ali, Zaringhalam Jalal
Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Basic Clin Neurosci. 2024 Sep-Oct;15(5):583-594. doi: 10.32598/bcn.2023.401.3. Epub 2024 Sep 1.
Alzheimer 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 (NFT), and neuron loss. Neurotrophic factors play a critical role in the treatment of AD. However, utilizing such neurotrophins has encountered certain difficulties and side effects. Novel technological advancements prioritize innovative dipeptide usage, which offers 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, to alleviate memory impairment in an intracerebroventricular single dose streptozotocin (STZ)-induced Alzheimer model in rats. We arranged 4 groups: Sham and groups receiving STZ and STZ + H-MGL (1 and 2 mg/kg). The H-MGL was administered consecutively for 14 days following the STZ injection. Then, the Morris water maze test was performed.
The findings suggest that administration of STZ caused a significantly increment in mean escape latency and mean traveled distance in acquisition days. H-MGL at a 1 mg/kg dosage failed to yield any notable improvement in rats compared to STZ. By contrast, 2 mg/kg of H-MGL dosage led to a significant decrease in the latency to first platform crossing and frequency of platform crossings.
Consequently, the findings above have engendered the notion that H-MGL partially ameliorates cognitive impairment, so it may hold promise for having low side effects to alleviate cognitive deficits in AD or potentially decrease the symptoms associated with its progression.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为记忆和认知功能逐渐衰退。它通过β淀粉样蛋白（Aβ）斑块的沉积、细胞内神经原纤维缠结（NFT）的积累以及神经元丢失来分类。神经营养因子在AD治疗中起关键作用。然而，使用此类神经营养素遇到了某些困难和副作用。新的技术进步优先考虑创新二肽的使用，其副作用较少。
本研究致力于分析一种新发现的神经营养素模拟二肽——六亚甲基二胺双（N-单琥珀酰-谷氨酰-赖氨酸）（实验室名称：H-MGL），以减轻大鼠脑室内单剂量链脲佐菌素（STZ）诱导的阿尔茨海默模型中的记忆损伤。我们设置了4组：假手术组以及接受STZ和STZ + H-MGL（1和2 mg/kg）的组。在STZ注射后连续14天给予H-MGL。然后，进行莫里斯水迷宫试验。
研究结果表明，给予STZ导致获取日的平均逃避潜伏期和平均游动距离显著增加。与STZ组相比，1 mg/kg剂量的H-MGL未能使大鼠有任何显著改善。相比之下，2 mg/kg剂量的H-MGL导致首次穿越平台的潜伏期和平台穿越频率显著降低。
因此，上述研究结果引发了这样一种观点，即H-MGL可部分改善认知障碍，因此它可能有望以低副作用缓解AD中的认知缺陷或潜在减轻与其进展相关的症状。
