Zhang Yawen, Ma Rui, Deng Qian, Wang Wencheng, Cao Chi, Yu Chunyang, Li Shulin, Shi Lei, Tian Jianying
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.
J Chem Neuroanat. 2023 Mar;128:102232. doi: 10.1016/j.jchemneu.2023.102232. Epub 2023 Jan 8.
Oxidative stress and neuroinflammation play crucial roles in aging. S-adenosylmethionine (SAM), a popular supplement, is a potential antioxidant and candidate therapy for depression. This study aimed to evaluate the neuroprotective effects of SAM on D-galactose-induced brain aging and explore its underlying mechanisms. Brain aging model was established with D-galactose (180 mg/kg/day) for 8 weeks. During the last 4 weeks, SAM (16 mg/kg) was co-administrated with D-galactose. Behavior tests were used to assess cognitive function and depression-like behaviors of rats. Results showed that cognitive impairment and depression-like behaviors were reversed by SAM. SAM reduced neuronal cell loss, increased brain-derived neurotrophic factor level in the hippocampus, inhibited amyloid-β level and microglia activation, as well as pro-inflammatory factors levels in the hippocampus and serum. Further, SAM enhanced antioxidant capacity and attenuated cholinergic damage by reducing malondialdehyde levels, increasing acetylcholine levels, expression levels of α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the hippocampus. Above all, SAM has a potential neuroprotective effect on ameliorating cognitive impairment in brain aging, which is related to inhibition of oxidative stress and neuroinflammation, as well as α7nAChR signals. DATA AVAILABILITY: Data will be made available on request.
氧化应激和神经炎症在衰老过程中起着关键作用。S-腺苷甲硫氨酸（SAM）是一种广受欢迎的补充剂，是一种潜在的抗氧化剂和抑郁症候选治疗药物。本研究旨在评估SAM对D-半乳糖诱导的脑衰老的神经保护作用，并探讨其潜在机制。用D-半乳糖（180mg/kg/天）建立脑衰老模型，持续8周。在最后4周，将SAM（16mg/kg）与D-半乳糖联合给药。采用行为测试评估大鼠的认知功能和抑郁样行为。结果表明，SAM可逆转认知障碍和抑郁样行为。SAM减少神经元细胞损失，增加海马中脑源性神经营养因子水平，抑制淀粉样β水平和小胶质细胞激活，以及海马和血清中的促炎因子水平。此外，SAM通过降低丙二醛水平、增加乙酰胆碱水平、海马中α7烟碱型乙酰胆碱受体（α7nAChR）、核因子红细胞2相关因子2（Nrf2）和血红素加氧酶1（HO-1）的表达水平，增强抗氧化能力并减轻胆碱能损伤。综上所述，SAM对改善脑衰老中的认知障碍具有潜在的神经保护作用，这与抑制氧化应激和神经炎症以及α7nAChR信号有关。数据可用性：数据将根据要求提供。
