Our previous study showed that datumetine modulates NMDAR activity with long term exposure leading to memory deficit and altered NMDAR signaling. We aim to explore the neurotransmitters perturbations of acute datumetine-NMDAR interaction. Fifteen C57/BL6 mice were used for the study, they are divided into three groups of 5 animals each. Animals were administered DMSO (DMSO/Control), 0.25 mg/kg body weight of datumetine (0.25 Datumetine) and 1 mg/kg bodyweight of datumetine (1.0 Datumetine) intraperitoneally for 14 days. At the end of treatment, animals were euthanized in isofluorane chamber, perfused transcardially with 1XPBS followed by PFA. Immunofluorescence procedure was done to check the distribution of neurons, astrocytes, microglia and major neuronal subtypes in the hippocampus. Expansion and electron microscopy techniques were used to assess the condition of the synapses. Quantitative data were expressed as mean ± SEM and analyzed using ANOVA with Tukey post hoc using p < 0.05 as significant. Datumetine increased the expression of CD11b, GFAP, vGlut1, GABA, CHRNA7 and TH while expression of TrPH and NeuN were reduced in the hippocampus compared to control animals. Synaptic loss was evident in datumetine exposed animals with reduced synaptic vesicles accompanied by a thickness of postsynaptic density than that of control animals. This study concludes that acute datumetine exposure alters hippocampal neurotransmitter systems.
Keywords: Datumetine; NMDARl excitotoxicity.