ABSTRACT Maternal exposure to imidacloprid (IMI) suppresses hippocampal neurogenesis in rat offspring. This study investigated the antioxidant effects of an amorphous formula of curcumin (CUR) given at a supplement level on IMI‐induced suppression of neurogenesis to clarify the toxicity mechanisms. Maternal rats were given a diet containing 750‐ppm IMI and drinking water with or without 120‐ppm CUR from gestational day (GD) 6 until weaning at 21 days post‐delivery. Then, offspring received CUR similarly until postnatal day 77 in adulthood. At weaning, IMI had suppressed neurogenesis and synaptic plasticity in granule cells, which may be related to suppressed reelin and parvalbumin signaling of GABAergic interneurons. IMI exposure increased CD68 + microglia, decreased CD163 + microglia, and upregulated Nos2 , suggesting M1 polarization; IMI also downregulated Tnf but did not change the transcript levels of other M1 cytokine genes, suggesting an immunocompromised state. IMI also suppressed hippocampal antioxidant capacity. CUR restored hippocampal antioxidant capacity and ameliorated neurogenesis and synaptic plasticity, involving parvalbumin + interneuron restoration through enhancing NMDAR2D‐mediated glutamatergic signaling. The IMI‐induced immunocompromised state and oxidative stress‐related effects disappeared in adulthood. However, IMI progressively suppressed neurogenesis, possibly associated with suppressed NMDAR2D‐mediated glutamatergic signaling. IMI also suppressed VGLUT2‐based glutamatergic signaling in granule cells. CUR increased synaptic plasticity in granule cells by enhancing VGLUT2‐based glutamatergic signaling and NMDAR2D‐mediated glutamatergic signaling. These results suggest that IMI continuously suppresses hippocampal neurogenesis and synaptic plasticity in granule cells into adulthood by increasing susceptibility to oxidative stress during exposure. CUR effectively ameliorated the IMI‐induced suppression of neurogenesis at weaning and synaptic plasticity until adulthood.
Ebizuka et al. (Thu,) studied this question.