PMID- 37346877
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231031
IS  - 2008-126X (Print)
IS  - 2228-7442 (Electronic)
IS  - 2008-126X (Linking)
VI  - 14
IP  - 1
DP  - 2023 Jan-Feb
TI  - Datumetine Preferentially Upregulates N-methyl-D-aspartate Receptor Signalling 
      Pathways in Different Brain Regions of Mice.
PG  - 103-116
LID - 10.32598/bcn.2021.3397.1 [doi]
AB  - 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 -20 degrees C 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 (CamKIIalpha) 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.
CI  - Copyright(c) 2023 Iranian Neuroscience Society.
FAU - Ishola, Azeez Olakunle
AU  - Ishola AO
AUID- ORCID: 0000-0001-9378-7858
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Adetunji, Adedeji Enitan
AU  - Adetunji AE
AUID- ORCID: 0000-0003-0532-252X
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Abanum, Isaac Chukwunwike
AU  - Abanum IC
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Adeyemi, Adesola Akorede
AU  - Adeyemi AA
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Faleye, Caleb Kenechukwu
AU  - Faleye CK
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Martins, Jane Babale
AU  - Martins JB
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Ogbe, Nnenna Chimdalu
AU  - Ogbe NC
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Ogundipe, Toluwalase Cherish
AU  - Ogundipe TC
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Okewulonu, Karen Ezichi
AU  - Okewulonu KE
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Okon, Umo Emmanuel
AU  - Okon UE
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Ovbude, Deborah Irenoise
AU  - Ovbude DI
AD  - Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola 
      University Ado-Ekiti, Nigeria.
FAU - Akele, Richard Yomi
AU  - Akele RY
AUID- ORCID: 0000-0003-2006-0820
AD  - Department of Medical Laboratory Science, College of Medicine and Health 
      Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.
FAU - Omotade, Naeemat Tolulope
AU  - Omotade NT
AD  - Department of Anatomy, College of Health Technology, Ijero-Ekiti, Nigeria.
FAU - Ajao, Moyosore Salihu
AU  - Ajao MS
AUID- ORCID: 0000-0002-9074-1405
AD  - Department of Anatomy, University of Ilorin, Ilorin, Nigeria.
LA  - eng
PT  - Journal Article
DEP - 20230101
PL  - Iran
TA  - Basic Clin Neurosci
JT  - Basic and clinical neuroscience
JID - 101575211
PMC - PMC10279986
OTO - NOTNLM
OT  - Cerebellum
OT  - Datumetine
OT  - Dizocilpine (MK-801)
OT  - Hippocampus
OT  - N-methyl-D-aspartate receptor (NMDAR)
OT  - Prefrontal cortex (PFC)
COIS- Conflict of interest The authors declared no conflict of interest.
EDAT- 2023/06/22 13:09
MHDA- 2023/06/22 13:10
PMCR- 2023/01/01
CRDT- 2023/06/22 09:56
PHST- 2021/05/13 00:00 [received]
PHST- 2021/06/15 00:00 [revised]
PHST- 2021/06/30 00:00 [accepted]
PHST- 2023/06/22 13:10 [medline]
PHST- 2023/06/22 13:09 [pubmed]
PHST- 2023/06/22 09:56 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - BCN-14-103 [pii]
AID - 10.32598/bcn.2021.3397.1 [doi]
PST - ppublish
SO  - Basic Clin Neurosci. 2023 Jan-Feb;14(1):103-116. doi: 10.32598/bcn.2021.3397.1. 
      Epub 2023 Jan 1.