title: The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus.
abstract: OBJECTIVE
  This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus.
  
  
  METHODS
  The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR.
  
  
  RESULTS
  Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P < 0.05). Interestingly, the DNA methylation of the BDNF exon IX was significantly increased in the ZD group, compared with the ZA and PF groups, whereas the expression of the BDNF mRNA was decreased. In addition, the DNMT1 mRNA expression was significantly upregulated and DNMT3A was downregulated in the ZD group, but not in the ZA and PF groups.
  
  
  CONCLUSIONS
  The learning and memory damage in offspring may be a result of the epigenetic changes of the BDNF genes in response to the zinc-deficient diet during 0∼2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency.
authors.affiliation: a Department of Nutrition , Tianjin Institute of Health and Environmental Medicine , Tianjin 300050 , China.|b Department of Nutrition and Food Hygiene , West China School of Public Health, Sichuan University , Chengdu 610041 , China.
authors.forename: Yan-Dan
authors.initials: YD
authors.lastname: Hu
authors.affiliation: a Department of Nutrition , Tianjin Institute of Health and Environmental Medicine , Tianjin 300050 , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.affiliation: c College of Life Science, Nan Kai University , Tianjin 300000 , China.
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: He
authors.affiliation: b Department of Nutrition and Food Hygiene , West China School of Public Health, Sichuan University , Chengdu 610041 , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.affiliation: a Department of Nutrition , Tianjin Institute of Health and Environmental Medicine , Tianjin 300050 , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: a Department of Nutrition , Tianjin Institute of Health and Environmental Medicine , Tianjin 300050 , China.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: c College of Life Science, Nan Kai University , Tianjin 300000 , China.
authors.forename: Yan-Qiang
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: b Department of Nutrition and Food Hygiene , West China School of Public Health, Sichuan University , Chengdu 610041 , China.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: a Department of Nutrition , Tianjin Institute of Health and Environmental Medicine , Tianjin 300050 , China.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000209:etiology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000235:genetics / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D003677:Deficiency Diseases / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism*; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D015032:Zinc / Q000097:blood / Q000172:deficiency* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619382:Dnmt1 protein, rat; D015032:Zinc
keywords: BDNF gene transcription; DNA methylation; Hippocampus; Learning and memory; Zinc deficiency