Effects of datumetine on hippocampal NMDAR activity

Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. [Display omitted] •Datura intoxication induces an amnesic experience.•N-methyl-d-aspartate receptor (NMDAR) is implicated in-memory processing.•Flexible docking showed datumetine binds with NMDAR...

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Published inToxicology reports Vol. 8; pp. 1131 - 1142
Main Authors Ishola, Azeez Olakunle, Imam, Aminu, Ajao, Moyosore Salihu
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.01.2021
Elsevier
Subjects
Datumetine
Datura
Docking
Hippocampus
NMDAR
Recent trends in environmental toxicology and sustainable agriculture
NMDAR
Docking
Datura
Datumetine
Hippocampus
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Abstract Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. [Display omitted] •Datura intoxication induces an amnesic experience.•N-methyl-d-aspartate receptor (NMDAR) is implicated in-memory processing.•Flexible docking showed datumetine binds with NMDAR.•Datumetine alters hippocampal NMDAR electrical activity.•Acute datumetine exposure alters NMDAR biological activity. The usage (abuse) of Datura metel is becoming increasingly worrisome among the Nigerian populace especially among the youth considering its side effects such as hallucination. This work was designed to identify the phytochemicals in datura plant that potentially interact with NMDAR as it affects the electrical and memory activities of the brain. Ligand-protein interaction was assessed using autodock vina to identify phytochemicals that can interact with NMDAR. Datumetine was found to have the best interaction fit with NMDAR at both allosteric and orthosteric binding sites. Furthermore, using electrophysiological, behavioural and western blotting techniques, it was observed that the administration of datumetine positively modulates the NMDAR current by prolonging burst duration and interspike interval, induces seizures in C57BL/6 mice. Acute exposure leads to memory deficit on NOR and Y-maze test while immunoblotting results showed increased expression of GluN1 and CamKIIα while pCamKIIα-T286, CREB and BDNF were downregulated. The results showed that the memory deficit seen in datura intoxication is possibly the effects of datumetine on NMDAR.
AbstractList The usage (abuse) of Datura metel is becoming increasingly worrisome among the Nigerian populace especially among the youth considering its side effects such as hallucination. This work was designed to identify the phytochemicals in datura plant that potentially interact with NMDAR as it affects the electrical and memory activities of the brain.Ligand-protein interaction was assessed using autodock vina to identify phytochemicals that can interact with NMDAR. Datumetine was found to have the best interaction fit with NMDAR at both allosteric and orthosteric binding sites. Furthermore, using electrophysiological, behavioural and western blotting techniques, it was observed that the administration of datumetine positively modulates the NMDAR current by prolonging burst duration and interspike interval, induces seizures in C57BL/6 mice. Acute exposure leads to memory deficit on NOR and Y-maze test while immunoblotting results showed increased expression of GluN1 and CamKIIα while pCamKIIα-T286, CREB and BDNF were downregulated. The results showed that the memory deficit seen in datura intoxication is possibly the effects of datumetine on NMDAR.
Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. • Datura intoxication induces an amnesic experience. • N -methyl- d -aspartate receptor (NMDAR) is implicated in-memory processing. • Flexible docking showed datumetine binds with NMDAR. • Datumetine alters hippocampal NMDAR electrical activity. • Acute datumetine exposure alters NMDAR biological activity. The usage (abuse) of Datura metel is becoming increasingly worrisome among the Nigerian populace especially among the youth considering its side effects such as hallucination. This work was designed to identify the phytochemicals in datura plant that potentially interact with NMDAR as it affects the electrical and memory activities of the brain. Ligand-protein interaction was assessed using autodock vina to identify phytochemicals that can interact with NMDAR. Datumetine was found to have the best interaction fit with NMDAR at both allosteric and orthosteric binding sites. Furthermore, using electrophysiological, behavioural and western blotting techniques, it was observed that the administration of datumetine positively modulates the NMDAR current by prolonging burst duration and interspike interval, induces seizures in C57BL/6 mice. Acute exposure leads to memory deficit on NOR and Y-maze test while immunoblotting results showed increased expression of GluN1 and CamKIIα while pCamKIIα-T286, CREB and BDNF were downregulated. The results showed that the memory deficit seen in datura intoxication is possibly the effects of datumetine on NMDAR.
Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. [Display omitted] •Datura intoxication induces an amnesic experience.•N-methyl-d-aspartate receptor (NMDAR) is implicated in-memory processing.•Flexible docking showed datumetine binds with NMDAR.•Datumetine alters hippocampal NMDAR electrical activity.•Acute datumetine exposure alters NMDAR biological activity. The usage (abuse) of Datura metel is becoming increasingly worrisome among the Nigerian populace especially among the youth considering its side effects such as hallucination. This work was designed to identify the phytochemicals in datura plant that potentially interact with NMDAR as it affects the electrical and memory activities of the brain. Ligand-protein interaction was assessed using autodock vina to identify phytochemicals that can interact with NMDAR. Datumetine was found to have the best interaction fit with NMDAR at both allosteric and orthosteric binding sites. Furthermore, using electrophysiological, behavioural and western blotting techniques, it was observed that the administration of datumetine positively modulates the NMDAR current by prolonging burst duration and interspike interval, induces seizures in C57BL/6 mice. Acute exposure leads to memory deficit on NOR and Y-maze test while immunoblotting results showed increased expression of GluN1 and CamKIIα while pCamKIIα-T286, CREB and BDNF were downregulated. The results showed that the memory deficit seen in datura intoxication is possibly the effects of datumetine on NMDAR.
Author Ishola, Azeez Olakunle
Ajao, Moyosore Salihu
Imam, Aminu
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CitedBy_id crossref_primary_10_1186_s42826_023_00162_7
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Keywords NMDAR
Docking
Datura
Datumetine
Hippocampus
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Snippet Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. [Display omitted] •Datura intoxication induces an...
Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. • Datura intoxication induces an amnesic experience. •...
The usage (abuse) of Datura metel is becoming increasingly worrisome among the Nigerian populace especially among the youth considering its side effects such...
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StartPage 1131
SubjectTerms Datumetine
Datura
Docking
Hippocampus
NMDAR
Recent trends in environmental toxicology and sustainable agriculture
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Title Effects of datumetine on hippocampal NMDAR activity
URI https://dx.doi.org/10.1016/j.toxrep.2021.05.009
https://search.proquest.com/docview/2543707050
https://pubmed.ncbi.nlm.nih.gov/PMC8190477
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