Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function
Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function
复制标题
DOI：
10.3390/nu11010176
复制
发表时间：
2019-01-01
期刊：
影响因子：
5.9
通讯作者：
Nah, Seung-Yeol
中科院分区：
文献类型：
--
作者：
Nam, Sung Min;Seo, Misun;Nah, Seung-Yeol
抗坏血酸是大脑正常发育和体内平衡所必需的。然而，抗坏血酸对成人大脑老化的影响尚未确定。高水平D-半乳糖（D-gal）的长期治疗通过累积氧化应激诱导脑老化。在本研究中，小鼠皮下给予D-半乳糖（150 mg/kg/天）10周;从第7周开始，口服抗坏血酸（150 mg/kg/天）共给药4周。虽然D-gal单独给药降低海马神经发生和认知功能，但抗坏血酸与D-gal的共同治疗通过改善细胞增殖、神经元分化和神经元成熟有效地防止了D-gal诱导的海马神经发生减少。长期D-gal治疗也降低了突触可塑性相关标志物的表达水平，即，突触素和磷酸化钙/钙调素依赖性蛋白激酶II，而抗坏血酸防止减少海马。此外，抗坏血酸改善D-半乳糖诱导的超氧化物歧化酶1和2，sirtuin 1，小窝蛋白-1，脑源性神经营养因子和上调白细胞介素1 β和肿瘤坏死因子α在海马下调。抗坏血酸介导的海马从D-半乳糖诱导的损伤中恢复与增强的海马依赖性记忆功能相关。因此，抗坏血酸通过抗氧化和抗炎作用改善D-半乳糖诱导的损伤，它可能是一种有效的膳食补充剂，对成人脑老化。
Ascorbic acid is essential for normal brain development and homeostasis. However, the effect of ascorbic acid on adult brain aging has not been determined. Long-term treatment with high levels of D-galactose (D-gal) induces brain aging by accumulated oxidative stress. In the present study, mice were subcutaneously administered with D-gal (150 mg/kg/day) for 10 weeks; from the seventh week, ascorbic acid (150 mg/kg/day) was orally co-administered for four weeks. Although D-gal administration alone reduced hippocampal neurogenesis and cognitive functions, co-treatment of ascorbic acid with D-gal effectively prevented D-gal-induced reduced hippocampal neurogenesis through improved cellular proliferation, neuronal differentiation, and neuronal maturation. Long-term D-gal treatment also reduced expression levels of synaptic plasticity-related markers, i.e., synaptophysin and phosphorylated Ca2+/calmodulin-dependent protein kinase II, while ascorbic acid prevented the reduction in the hippocampus. Furthermore, ascorbic acid ameliorated D-gal-induced downregulation of superoxide dismutase 1 and 2, sirtuin1, caveolin-1, and brain-derived neurotrophic factor and upregulation of interleukin 1 beta and tumor necrosis factor alpha in the hippocampus. Ascorbic acid-mediated hippocampal restoration from D-gal-induced impairment was associated with an enhanced hippocampus-dependent memory function. Therefore, ascorbic acid ameliorates D-gal-induced impairments through anti-oxidative and anti-inflammatory effects, and it could be an effective dietary supplement against adult brain aging.