Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid.
Experiments in rodents have indicated that maternal valproic acid (VPA) exposure has permanent adverse effects upon neurological and behavioral development. In humans, prenatal exposure to VPA can induce fetal valproate syndrome, which has been associated with autism. The present study examined mouse pups exposed in utero to VPA, measuring physical development, olfactory discrimination, and social behavior as well as expression of plasticity-related genes, brain derived neurotrophic factor (BDNF) and NMDA receptor subunits NR2A and NR2B. VPA-exposed mice showed delayed physical development, impaired olfactory discrimination, and dysfunctional pre-weaning social behavior. In situ hybridization experiments revealed lower cortical expression of BDNF mRNA in VPA animals. These results support the validity of the VPA mouse model for human autism and suggest that alterations in plasticity-related genes may contribute to the behavioral phenotype.
Roullet
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FI
Department of Psychiatry and Behavioural Neurosciences, McMaster University, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6 - Canada.
Wollaston
L
L
Decatanzaro
D
D
Foster
J A
JA
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001321:Autistic Disorder / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000523:psychology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014635:Valproic Acid / Q000633:toxicity*
D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D014635:Valproic Acid; C121001:NR2B NMDA receptor