Wong-Guerra Maylin, Jiménez-Martin Javier, Fonseca-Fonseca Luis Arturo, Ramírez-Sánchez Jeney, Montano-Peguero Yanay, Rocha Joao Batista, D Avila Fernanda, de Assis Adriano M, Souza Diogo Onofre, Pardo-Andreu Gilberto L, Del Valle Roberto Menéndez-Soto, Lopez Guillermo Aparicio, Martínez Odalys Valdés, García Nelson Merino, Mondelo-Rodríguez Abel, Padrón-Yaquis Alejandro Saúl, Nuñez-Figueredo Yanier
a Laboratorio de Neurofarmacología Molecular , Centro de Investigación y Desarrollo de Medicamentos , La Habana , Cuba.
b Department of Physiology, Otago School of Medical Sciences , University of Otago , Dunedin , New Zealand.
Neurol Res. 2019 May;41(5):385-398. doi: 10.1080/01616412.2019.1573285. Epub 2019 Mar 1.
JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages.
The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined.
The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions.
The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deficits associated with AD in humans.
据报道，新型杂合合成分子JM-20具有抗氧化、线粒体保护、抗兴奋毒性、抗凋亡和抗炎特性。然而，尚未分析JM-20在临床前类阿尔茨海默病模型中对记忆障碍的神经保护作用。本研究的目的是评估JM-20的潜在神经保护作用，其可保护基本记忆过程免受胆碱能功能障碍和其他分子损伤。
研究了JM-20对东莨菪碱（1 mg/kg）诱导的认知障碍的影响。用JM-20和/或东莨菪碱处理雄性Wistar大鼠（220-230 g），并进行行为测试。采用分光光度法测定脑组织中的乙酰胆碱酯酶活性、超氧化物歧化酶活性、过氧化氢酶活性、丙二醛和总巯基水平。行为测试后测量线粒体功能参数。用苏木精和伊红对海马和前额叶皮质进行组织学分析，并确定神经元和轴突损伤情况。
行为、生化和组织病理学研究表明，JM-20（8 mg/kg）口服预处理可显著减轻东莨菪碱诱导的记忆缺陷、线粒体功能障碍、氧化应激，并可能通过特异性抑制乙酰胆碱酯酶预防乙酰胆碱酯酶活性过高。还观察到对海马和前额叶皮质区域有明显的组织学保护作用。
该分子的多模式作用可能介导了此处观察到的记忆保护作用，并表明它可能调节与人类阿尔茨海默病相关的记忆缺陷的不同病理方面。
