Datumetine Preferentially Upregulates NMDAR Signalling Pathways in Different Brain Regions of Mice

Abstract

Background: We earlier reported that datumetine possesses binding affinity with NMDAR and that 14-day exposure to datumetine altered NMDAR signalling by mimicking glutamate toxicity. Here, we investigated the potential neuroprotective effect of a single shot of a low dose of datumetine administration in BALB/c mice. Results: Relative to Veh, datumetine downregulate the expression of CamKIIα in the hippocampus and PFC but not in the cerebellum, CREB was also upregulated in the PFC only, but pCREB was also upregulated in all the three brain regions observed, while BDNF was only upregulated in both hippocampus and PFC of Datumetine relative to Veh. MK-801 on the other hand reversed some of the effects of datumetine in the brain regions observed. No major histological alterations were observed in the different brain regions immunohistochemically. Conclusion: We conclude that a single low dose of datumetine moderately enhances NMDAR activity. This showed the neuroprotective potentials of low datumetine exposure.