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Effects of datumetine on hippocampal NMDAR activity.

ABSTRACT: 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.

SUBMITTER: Ishola AO

PROVIDER: S-EPMC8190477 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Hippocampal Lnx1-NMDAR multiprotein complex mediates initial social memory.

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| S-EPMC8550978 | biostudies-literature

Effects of NMDAR on mouse hippocampal neuron (HT22) mRNA and lncRNA expression during hypoxia/reoxygenation injury

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2022-10-10 | GSE214716 | GEO

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| S-SCDT-EMBOJ-2020-105513 | biostudies-other

Fractalkine (CX3CL1) enhances hippocampal N-methyl-D-aspartate receptor (NMDAR) function via D-serine and adenosine receptor type A2 (A2AR) activity.

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GSK3α, not GSK3β, drives hippocampal NMDAR-dependent LTD via tau-mediated spine anchoring.

Project description:Glycogen synthase kinase-3 (GSK3) is an important signalling protein in the brain and modulates different forms of synaptic plasticity. Neuronal functions of GSK3 are typically attributed to one of its two isoforms, GSK3β, simply because of its prevalent expression in the brain. Consequently, the importance of isoform-specific functions of GSK3 in synaptic plasticity has not been fully explored. We now directly address this question for NMDA receptor-dependent long-term depression (LTD) in the hippocampus. Here, we specifically target the GSK3 isoforms with shRNA knock-down in mouse hippocampus and with novel isoform-selective drugs to dissect their roles in LTD. Using electrophysiological and live imaging approaches, we find that GSK3α, but not GSK3β, is required for LTD. The specific engagement of GSK3α occurs via its transient anchoring in dendritic spines during LTD induction. We find that the major GSK3 substrate, the microtubule-binding protein tau, is required for this spine anchoring of GSK3α and mediates GSK3α-induced LTD. These results link GSK3α and tau in a common mechanism for synaptic depression and rule out a major role for GSK3β in this process.

| S-EPMC7809792 | biostudies-literature

Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model.

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| S-EPMC8088363 | biostudies-literature

Effects of NMDAR on mouse hippocampal neuron (HT22) proteome expression during hypoxia/reoxygenation injury

Project description:Brain tissue is extremely sensitive to hypoxia/reoxygenation (H/R) injury, which can easily cause irreversible damage to neurons. H/R injury could induce neuronal apoptosis through glutamate-mediated excitotoxicity. N-methyl-d-aspartate receptor (NMDAR) is one of the main receptors of excitatory glutamate, and blocking NMDAR could protect brain tissue from ischemia and hypoxia injury. NMDAR hypofunction can also cause psychotic symptoms or cognitive impairment. However, there is still a lack of systematic research on the changes of the proteome and transcriptome in neuronal cells under the condition of NMDAR hypofunction and H/R injury. In this study, we compared the changes of proteome expression levels in neurons after NMDAR knockdown and H/R stimulation by isobaric tags for relative and absolute quantitation (iTRAQ).

2022-08-24 | PXD036251 |

Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory.

Project description:N-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, both in vitro in primary cultured hippocampal neurons and in vivo in adult male Wistar rats. After in vitro characterization, we performed a cognitive profile and evaluated seizure susceptibility in vivo. Our in vitro results showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNA in vivo displayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning-memory mechanisms.

| S-EPMC8064689 | biostudies-literature

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