title: Folic acid deficiency increases brain cell injury via autophagy enhancement after focal cerebral ischemia.
abstract: Folic acid (FA) deficiency is not only associated with an increased risk of ischemic stroke, but also with increased oxidative DNA damage and brain injury after cerebral ischemia-reperfusion. However, the cellular and molecular mechanisms underlying FA deficiency-associated neuropathogenesis are not completely understood. In the present study, we tested the hypothesis that neuronal autophagy in focal cerebral ischemia rats may be involved in the mechanisms of FA deficiency-induced injury to neuronal cells. The results demonstrated that, accompanied by obvious neuron damage, the expression of the autophagic markers LC3 and Beclin-1, and the formation of 8-OHdG (a marker of oxidative stress to DNA) and autophagosomes were significantly increased in the brain cortex after ischemia-reperfusion. FA deficiency further induced neuronal cell death, and significantly increased the formation of autophagosomes and the expression of LC3 and Beclin-1 in NeuN-positive cell bodies after ischemia-reperfusion. The elevated level of 8-OHdG was also observed in the ischemic cortex of FA deficiency-treated animals. Conversely, the neuronal cell injury, autophagosome accumulation and the effects of LC3 and Beclin1 overexpression caused by FA deficiency were partially blocked by an autophagic inhibitor 3-methyladenine. These results suggest that FA deficiency progresses autophagic activation and aggravates the damage in rat brain cortex following focal cerebral ischemia-reperfusion. The oxidative injury may be involved in cell morphological damage and autophagy alteration caused by FA deficiency.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China. Electronic address: zhangxumei@tmu.edu.cn.
authors.forename: Xumei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D066146:Cell Body / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004249:DNA Damage / Q000187:drug effects; D005494:Folic Acid Deficiency / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000225:Adenine; D000071186:Beclin-1; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C025946:3-methyladenine
keywords: Autophagy; Cerebral ischemia–reperfusion; Cortex; Folic acid deficiency; Oxidative stress