Datumetine Preferentially Upregulates N-methyl-D-aspartate Receptor Signalling Pathways in Different Brain Regions of Mice
Authors:   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Olakunle Ishola Azeez , Enitan Adetunji Adedeji ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Chukwunwike Abanum Isaac ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Akorede Adeyemi Adesola ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Kenechukwu Faleye Caleb ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Babale Martins Jane ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Chimdalu Ogbe Nnenna ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Cherish Ogundipe Toluwalase ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Ezichi Okewulonu Karen ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Emmanuel Okon Umo ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Irenoise Ovbude Deborah ,   Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University Ado-Ekiti, Nigeria., Yomi Akele Richard ,   Department of Medical Laboratory Science, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria., Tolulope Omotade Naeemat ,   Department of Anatomy, College of Health Technology, Ijero-Ekiti, Nigeria., Salihu Ajao Moyosore ,   Department of Anatomy, University of Ilorin, Ilorin, Nigeria.
Published: July 2021

Introduction: We previously reported that datumetine possesses binding affinity with N-methyl-D-aspartate receptor (NMDAR) and that 14-day exposure to datumetine altered NMDAR signaling 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. Methods: 30 male adult BALB/c mice were used for the study. The mice were randomly divided into three groups of ten mice each with an intraperitoneal injection of 0.1 mL of 10% DMSO for the Vehicle group, Datumetine group were administered 0.1 mg/kg body weight (bw) of datumetine and MK-801+Datumetine group were administered 0.5 mg/kg bw of MK-801 (to block NMDAR) followed by 0.1 mg/kg bw of datumetine after 30 minutes. 24 hours after administration, mice were euthanized in an isoflurane chamber followed by perfusion with 1X PBS. Brains were excised and stored at -200C till further processing. Mice designated for IHC were further perfused with 4% PFA and brain excised and stored in 4% PFA till further processing. NMDAR signalling molecules expression was evaluated in frozen brain samples and the fixed brain samples were stained for neuron, vGlut and NMDAR subtypes. Results: Relative to vehicle (Veh), datumetine downregulate calcium calmodulin kinase II alpha (CamKIIα) expression in the hippocampus and prefrontal cortex (PFC) but not in the cerebellum, cyclic AMP response element binding protein (CREB) was also upregulated only in the PFC but phosphorylated CREB (pCREB) was also upregulated in three brain regions observed, while brain-derived neurotrophic factor (BDNF) was only upregulated in hippocampus and PFC of Datumetine relative to vehicle (Veh). On the other hand, dizocilpine (MK-801) reversed some of the effects of datumetine in the observed brain regions. No major histological alterations were observed in the different brain regions immunohistochemically. Conclusion: We conclude that a low dose of datumetine moderately enhances NMDAR activity. This showed the neuroprotective potentials of low datumetine exposure.