Laboratorio de Neurofarmacología Experimental, Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Ave 26 No. 1605 Boyeros y Puentes Grandes, La Habana, 10600, Cuba.
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, USACH, Santiago, Alameda, 3363, Chile.
Neurochem Res. 2024 Nov 15;50(1):8. doi: 10.1007/s11064-024-04254-1.
The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer's disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8 mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8 mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging.
与衰老相关的认知功能下降显著影响老年人及其家庭的幸福感。这种下降是神经退行性疾病(尤其是阿尔茨海默病)的一个主要公认风险因素。衰老动物模型为评估药物提供了一个平台,可评估药物在记忆和氧化应激等方面的作用。JM-20 已被证明对短期记忆获得和巩固具有保护作用,具有抗氧化特性,并能调节乙酰胆碱酯酶活性。本研究评估了 JM-20 对认知能力下降和与年龄相关的记忆丧失的潜在保护作用。在这项研究中,首先选择了表现出与衰老相关损伤的老年小鼠。然后形成实验分组,评估 8mg/kg 的 JM-20 对与衰老相关的行为(如空间记忆、新颖性识别记忆、活动能力和焦虑)的影响,为期 40 天。随后,处死动物并提取海马区进行氧化还原研究,以评估乙酰胆碱酯酶活性。结果表明,8mg/kg 的 JM-20 逆转了空间工作和参考记忆的损伤,表现出与未处理的年轻成年动物相当的性能。此外,JM-20 保留了超氧化物歧化酶、过氧化氢酶和总巯基水平的酶活性,防止了与年龄相关的认知障碍,表明其对大脑水平的氧化事件具有强大的保护作用。然而,只有年轻健康的动物表现出乙酰胆碱酯酶活性降低。这些发现为 JM-20 的神经保护活性提供了临床前药理学证据,使其成为治疗与衰老相关的记忆障碍的有希望的治疗候选药物。