Gene expression profiles of multiple brain regions in rats differ between developmental and postpubertal exposure to valproic acid. Issue 5 (14th November 2021)

• Record Type: Journal Article
• Authors: Ojiro, Ryota; Watanabe, Yousuke; Okano, Hiromu; Takahashi, Yasunori; Takashima, Kazumi; Tang, Qian; Ozawa, Shunsuke; Saito, Fumiyo; Akahori, Yumi; Jin, Meilan; Yoshida, Toshinori; Shibutani, Makoto
• Is Part Of: Journal of applied toxicology. Volume 42:Issue 5(2022)
• Page Start: 864
• Page End: 882
• Publication Date: 2021-11-14
• Subjects: cerebellar vermis -- cerebral cortex -- corpus callosum -- developmental exposure -- hippocampal dentate gyrus -- microarray -- postpubertal 28‐day exposure -- rat -- valproic acid; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4263
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: We have previously reported that the valproic acid (VPA)‐induced disruption pattern of hippocampal adult neurogenesis differs between developmental and 28‐day postpubertal exposure. In the present study, we performed brain region‐specific global gene expression profiling to compare the profiles of VPA‐induced neurotoxicity between developmental and postpubertal exposure. Offspring exposed to VPA at 0, 667, and 2000 parts per million (ppm) via maternal drinking water from gestational day 6 until weaning (postnatal day 21) were examined, along with male rats orally administered VPA at 0, 200, and 900 mg/kg body weight for 28 days starting at 5 weeks old. Four brain regions—the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis—were subjected to expression microarray analysis. Profiled data suggested a region‐specific pattern of effects after developmental VPA exposure, and a common pattern of effects among brain regions after postpubertal VPA exposure. Developmental VPA exposure typically led to the altered expression of genes related to nervous system development ( Msx1, Xcl1, Foxj1, Prdm16, C3, and Kif11 ) in the hippocampus, and those related to nervous system development ( Neurod1 ) and gliogenesis ( Notch1 and Sox9 ) in the corpus callosum. Postpubertal VPA exposure led to the altered expression of genes related to neuronal differentiation and projection ( Cd47, Cyr61, Dbi, Adamts1, and Btg2 ) in multiple brain regions. These findings suggested that neurotoxic patterns of VPA might be different between developmental and postpubertal exposure, which was consistent with our previous study. Of note, the hippocampal dentate gyrus might be a sensitive target of developmental neurotoxicants after puberty. Abstract : Global gene expression profiling was performed in four different brain regions in rats after developmental or postpubertal 28‐day valproic acid (VPA) exposure. Developmental VPA exposure had specific effects on each of the four brain regions, while postpubertal VPA exposure had common effects among multiple brain regions. Our results suggested that the neurotoxic pattern of VPA might differ between developmental and postpubertal exposure. They also suggested that the hippocampal dentate gyrus might be particularly vulnerable to postpubertal exposure to developmental neurotoxicants.