title: Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid.
abstract: Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction.
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China; Department of Nursing, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China.
authors.forename: Jingquan
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Physiology, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Child Health Care, Harbin children's hospital, Harbin, Heilongjiang, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China. Electronic address: 523418346@qq.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: wulijiehyd@126.com.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects* / Q000737:chemistry; D001522:Behavior, Animal / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D007859:Learning Disabilities / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017208:Rats, Wistar; D012919:Social Behavior; D014635:Valproic Acid / Q000009:adverse effects* / Q000037:antagonists & inhibitors
chemical_list: D000927:Anticonvulsants; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D014635:Valproic Acid
keywords: Docosahexaenoic acid (DHA); Learning; Maternal feeding; Memory; Valproic acid (VPA)