title: Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid.
abstract: Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development.
authors.affiliation: Joint Program in Toxicology, Rutgers, The State University of New Jersey, 152 Frelinghyusen Road, Piscataway, NJ 08854, USA.
authors.forename: Melody A
authors.initials: MA
authors.lastname: Furnari
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghyusen Road, Piscataway, NJ 08854, USA.
authors.forename: Constance Lay-Lay
authors.initials: CL
authors.lastname: Saw
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghyusen Road, Piscataway, NJ 08854, USA.
authors.forename: Ah-Ng
authors.initials: AN
authors.lastname: Kong
authors.affiliation: Department of Psychology, Rutgers, The State University of New Jersey, 152 Frelinghuysen Road, New Brunswick, NJ 08854, USA. Electronic address: gcwagner@rci.rutgers.edu.
authors.forename: George C
authors.initials: GC
authors.lastname: Wagner
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000235:genetics*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014635:Valproic Acid
keywords: Developmental behavior; Knockout mice; Nrf2; Rotorod; Valproic acid; Water maze