λ-cyhalothrin induced sex-specific inflammation, glia activation and GABAergic interneuron disruption in the hippocampus of rats

Abstract

<title>Abstract</title> Background Glia mediated neuroinflammation and degeneration of inhibitory GABAergic interneurons are some of the hall marks of pyrethroid neurotoxicity. Here we investigated the sex specific responses of inflammatory cytokines, microglia, astrocyte and parvalbumin positive inhibitory GABAergic interneurons to λ-cyhalothrin (LCT) exposures in rats. Methods Equal numbers of male and female rats were given oral corn oil, 2 mg/kg.bw and 4 mg/kg.bw of LCT for fourteen days. They were euthanized on day 15, brains were excised and hippocampus (n = 5/group) isolated for interleukin 1 beta (IL-1β) and tumor necrotic factor alpha (TNF-α) analysis. The remaining brains (n = 3/group) were processed for Ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP) and parvalbumin (PV) expressions in the hippocampus. All quantitative data was subjected to one way analysis of variance (ANOVA). Results LCT caused sex and dose dependent increase in IL-1β and TNF-α concentrations, activated microglia (IBA1+) and reactive astrocyte (GFAP+) expressions, but depleted PV + GABAergic interneurons. These effects were greater in males compared to females, and dose-dependent in both sexes. Conclusion LCT specifically induced inflammation and disrupted GABAergic interneurons’ integrities via activation of microglia and reactive astrogliosis and such effects are dose-dependent and sexually dimorphic.