Research reportAltered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid

•Nrf2 knockout mice perform similarly to wild type mice in developmental behavioral assays.•Exposure to VPA on postnatal day 14 results in behavioral deficits in wild type and Nrf2 null mice.•Nrf2 knockout mice were more sensitive to VPA as seen in the rotorod and water maze.

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.