PI3K/Akt/GSK3β induced CREB activation ameliorates arsenic mediated alterations in NMDA receptors and associated signaling in rat hippocampus: Neuroprotective role of curcumin

    loading  Checking for direct PDF access through Ovid


HIGHLIGHTSProtective role of curcumin in arsenic induced NMDA receptor alterations investigated.Sodium arsenite decreased expression of BDNF, pAkt, pErk ½, pGSK3β and pCREB.Curcumin protected sodium arsenite induced changes via PI3/Akt/MAPK pathway in hippocampus.Impaired cognitive deficits by sodium arsenite in rats also recovered by curcumin.Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3K/Akt/ GSK3β signalling in hippocampus has been investigated in vivo and in vitro. Exposure to sodium arsenite (in vivo – 20mg/kg, body weight p.o. for 28 days; in vitro – 10μM for 24h) and curcumin (in vivo – 100mg/kg body weight p.o. for 28 days; in vitro – 20μM for 24h) was carried out alone or simultaneously. Treatment with curcumin ameliorated sodium arsenite induced alterations in the levels of NMDA receptors, its receptor subunits and synaptic proteins - pCaMKIIα, PSD-95 and SynGAP both in vivo and in vitro. Decreased levels of BDNF, pAkt, pERK1/2, pGSK3β and pCREB on sodium arsenite exposure were also protected by curcumin. Curcumin was found to decrease sodium arsenite induced changes in hippocampus by modulating PI3K/Akt/GSK3β neuronal survival pathway, known to regulate various cellular events. Treatment of hippocampal cultures with pharmacological inhibitors for ERK1/2, GSK3β and Akt individually inhibited levels of CREB and proteins associated with PI3K/Akt/GSK3β pathway. Simultaneous treatment with curcumin was found to improve sodium arsenite induced learning and memory deficits in rats assessed by water maze and Y-maze. The results provide evidence that curcumin exercises its neuroprotective effect involving PI3K/Akt pathway which may affect NMDA receptors and downstream signalling through TrKβ and BDNF in arsenic induced cognitive deficits in hippocampus.

    loading  Loading Related Articles