Nam, Sung Min Seo, Misun Seo, Jin-Seok Rhim, Hyewhon Nahm, Sang-Soep Cho, Ik-Hyun Chang, Byung-Joon Kim, Hyeon-Joong Choi, Sun-Hye Nah, Seung-Yeol 2024-01-19T21:03:32Z 2024-01-19T21:03:32Z 2021-09-04 2019-01 2072-6643 https://pubs.kist.re.kr/handle/201004/120542 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. English Multidisciplinary Digital Publishing Institute (MDPI) Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function Article 10.3390/nu11010176 1 Nutrients, v.11, no.1 Nutrients 11 1 Y scie scopus 000457477800007 2-s2.0-85060150728 Nutrition & Dietetics Nutrition & Dietetics Article OXIDATIVE STRESS VITAMIN-C NEUROBLAST DIFFERENTIATION SYNAPTIC PLASTICITY CELL-PROLIFERATION RAT IMPAIRMENT DEFICITS DAMAGE MICE ascorbic acid D-galactose hippocampus brain aging neurogenesis