Extenuation of in utero toxic effects of MeHg in the developing neurons by Fisetin via modulating the expression of synaptic transmission and plasticity regulators in hippocampus of the rat offspring.

The neurotoxic environmental contaminant, methylmercury (MeHg), has shown to have detrimental effects on the developing brain when exposed during gestation. We have shown in our earlier studies that gestational administration of 3,3',4',7-Tetrahydroxyflavone or Fisetin reduces the toxic effects of MeHg in the developing rat brain. The current study has pivoted to study the mechanism behind the mitigating action of Fisetin against prenatal MeHg exposure induced neurotoxicity. Negligible data is available about the toxicity targets of MeHg in the developing brain. Studies have exhibited that MeHg exposure cause toxic effects on synaptic transmission and plasticity in the offspring brain. Hence, we aimed to study the effect of Fisetin on MeHg induced alterations in the expressions of regulatory genes and proteins involved in synaptic plasticity and transmission. Pregnant rats were grouped according to the type of oral administration as, (i) Control, (ii) MeHg (1.5 mg/kg b. w.), (iii) MeHg + Fisetin (30 mg/kg b. w.) and (iv) Fisetin (30 mg/kg b. w). Maternal administration of Fisetin prevented MeHg exposure induced downregulation of neurogranin (Nrgn), dendrin (Ddn), Syntaxin 1 A (Stx1a), Lin-7 homolog A (Lin7a), Complexin-2 (Cplx2) and Exocyst complex component 8 (Exoc8) genes in the offspring rat. Fisetin also prevented MeHg exposure induced downregulation of brain derived neurotrophic factor (BDNF), Glial-cell derived neurotrophic factor (GDNF) protein expressions and hampered reactive astrogliosis in the hippocampus of F generation rats. Hence, through this study, we conclude that Fisetin modulates the expression of regulatory genes and proteins involved in synaptic transmission and plasticity and extenuates MeHg neurotoxicity in the developing rat brain.