Ameliorating effect of α-glycosyl isoquercitrin treatment from gestation on disruption of hippocampal neurogenesis induced by maternal exposure to imidacloprid in rats.

There is a growing concern about developmental brain impairment following exposure to neonicotinoid pesticides. Experimentally, imidacloprid (IMI), a representative neonicotinoid pesticide, impairs postnatal hippocampal neurogenesis in rat offspring after maternal exposure. This study examined how IMI disrupts neurogenesis and whether the synthetic flavonoid α-glycosyl isoquercitrin (AGIQ) can counteract these effects through its antioxidant action. Maternal rats were given a diet containing 750 ppm IMI and drinking water with or without 0.3% AGIQ from gestation day 6 until weaning on day 21 post-delivery. Then, male offspring similarly received AGIQ until postnatal day 77 or 79 during adulthood. Continuous AGIQ exposure restored IMI-suppressed neurogenesis and proliferation of neural progenitor cells, granule cell synaptic plasticity, the numbers of reelin+ and calbindin-D-29K+ GABAergic interneurons, and BDNF-TrkB signaling in the dentate gyrus at weaning, improving spatial memory. In adulthood, AGIQ also reversed IMI-induced persistent deficits in neurogenesis, synaptic plasticity, and BDNF-TrkB signaling. AGIQ normalized the IMI-induced immunocompromised state (evidenced by downregulation of pro-inflammatory cytokine genes but an increase in the number of pro-inflammatory microglia/macrophages) by increasing acetylcholinesterase activity at weaning. AGIQ also recovered the IMI-induced suppression of antioxidant capacity observed at weaning by restoring antioxidant gene expression and elevating the reduced glutathione/oxidized glutathione ratio in adulthood. Overall, maternal IMI exposure caused immunosuppression and heightened oxidative stress sensitivity in the dentate gyrus, disrupting neurogenesis and synaptic plasticity through suppression of the BDNF-TrkB pathway, as well as reelin and calbindin-D-29K+ interneuron signaling. AGIQ mitigated IMI-induced hippocampal immunosuppression and antioxidant system damage by enhancing acetylcholinesterase activity and antioxidant gene expression.