title: Folic acid enhances Notch signaling, hippocampal neurogenesis, and cognitive function in a rat model of cerebral ischemia.
abstract: Increasing neurogenesis may restore cognitive functions that are impaired in ischemia stroke. Folic acid has been reported to play an important role in neuronal development and reduce the risk of ischemic stroke in primary prevention. Folic acid supplementation stimulates Notch signaling  and cell proliferation in neural progenitor cells cultured from neonatal brain. The present study determined whether folic acid supplementation stimulates Notch signaling and neurogenesis and improves cognitive function after ischemic stroke in adult brain. Rats were randomly assigned to four  groups: sham operation plus vehicle (Sham), middle cerebral artery occlusion plus vehicle (MCAO), MCAO plus low-dose folic acid (4 mg/(kg day)), and MCAO plus high folic acid (12 mg/(kg day)). The vehicle and folic acid were administered by oral gavage for 28 days prior  to sham or MCAO operation and up to 14 days after surgery. Newborn hippocampal neurons were detected at 3, 7, and 14 days post-MCAO. Cognitive function (learning and memory in Y-maze tests) and the protein expression levels of components of the Notch signaling system (Notch1, Hes1, and Hes5)  were measured at 7 days post-MCAO. The results showed that MCAO impaired Y-maze performance and stimulated Notch signaling and hippocampal neurogenesis in brain. Folic acid prevented the impairment of Y-maze performance. The nutrient also increased further the expression of Notch1, Hes1, and  Hes5 and the number of the newborn hippocampal neurons. Folic acid enhances the stimulation by ischemia of Notch signaling and hippocampal neurogenesis in adult brain and lessens the impairment of cognitive function that occurs after experimental stroke.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Xumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: John X
authors.initials: JX
authors.lastname: Wilson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005492:Folic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020521:Stroke / Q000188:drug therapy; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005492:Folic Acid; D018398:Homeodomain Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C489686:Hes5 protein, rat; C497763:Notch1 protein, rat