Effects of datumetine on hippocampal NMDAR activity
| Autor: | Moyosore Salihu Ajao, Aminu Imam, Azeez Olakunle Ishola |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Health
Toxicology and Mutagenesis Allosteric regulation Hippocampus 010501 environmental sciences Hippocampal formation Toxicology CREB 01 natural sciences Docking 03 medical and health sciences 0302 clinical medicine RA1190-1270 mental disorders Datumetine 0105 earth and related environmental sciences biology musculoskeletal neural and ocular physiology Recent trends in environmental toxicology and sustainable agriculture biology.organism_classification NMDAR Blot Electrophysiology nervous system Toxicology. Poisons biology.protein Datura NMDA receptor biological phenomena cell phenomena and immunity Datura metel Neuroscience psychological phenomena and processes 030217 neurology & neurosurgery |
| Zdroj: | Toxicology Reports, Vol 8, Iss, Pp 1131-1142 (2021) Toxicology Reports |
| ISSN: | 2214-7500 |
| DOI: | 10.1016/j.toxrep.2021.05.009 |
| Popis: | Graphical abstract Datumetine binds with NMDAR altering its calcium current. Acute exposure downregulates NMDAR signalling. Highlights • 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. |
| Databáze: | OpenAIRE |
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