Effect of Pharmacological Modulation of Activity of Metabotropic Glutamate Receptors on Their Gene Expression after Excitotoxic Damage in Hippocampal Neurons

Першина, Е. В.; Kapralova, M. V.; Архипов, В. И.

doi:10.1007/s10517-017-3713-2

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…According to a recent study involving KA-induced excitotoxic hippocampal neuronal damage in rats, 2-Methyl-6-(phenylethynyl)-pyridine (a negative allosteric modulator of mGluR5) and LY354740 (an agonist of mGluR2) treatments ameliorate KA-induced neuronal cell death. Based on these results, both KARs and mGluRs may be involved in the KA-induced neuronal toxicity (Pershina et al, 2017). …”

Section: Glutamate Receptors As Potential Targets In Neurotoxic Agentmentioning

confidence: 99%

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Jakaria

Park

Haque

et al. 2018

Front. Mol. Neurosci.

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Glutamate receptors play a crucial role in the central nervous system and are implicated in different brain disorders. They play a significant role in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Although many studies on NDDs have been conducted, their exact pathophysiological characteristics are still not fully understood. In in vivo and in vitro models of neurotoxic-induced NDDs, neurotoxic agents are used to induce several neuronal injuries for the purpose of correlating them with the pathological characteristics of NDDs. Moreover, therapeutic drugs might be discovered based on the studies employing these models. In NDD models, different neurotoxic agents, namely, kainic acid, domoic acid, glutamate, β-N-Methylamino-L-alanine, amyloid beta, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, rotenone, 3-Nitropropionic acid and methamphetamine can potently impair both ionotropic and metabotropic glutamate receptors, leading to the progression of toxicity. Many other neurotoxic agents mainly affect the functions of ionotropic glutamate receptors. We discuss particular neurotoxic agents that can act upon glutamate receptors so as to effectively mimic NDDs. The correlation of neurotoxic agent-induced disease characteristics with glutamate receptors would aid the discovery and development of therapeutic drugs for NDDs.

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Section: Glutamate Receptors As Potential Targets In Neurotoxic Agentmentioning

confidence: 99%

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Jakaria

Park

Haque

et al. 2018

Front. Mol. Neurosci.

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“…To date, eight subtypes of mGluRs have been characterized, which are divided into three groups based on their sequence homology, involved cell signaling pathways, and agonist selectivity [7]. Some mGluR ligands were shown to have neuroprotective effects in vivo [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus

Першина

Chernomorets

Fedorov

et al. 2023

IJMS

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We studied the neuroprotective properties of the non-competitive NMDA receptor antagonist memantine, in combination with a positive allosteric modulator of metabotropic glutamate receptors of Group III, VU 0422288. The treatment was started 48 h after the injection of neurotoxic agent trimethyltin (TMT) at 7.5 mg/kg. Three weeks after TMT injection, functional and morphological changes in a rat hippocampus were evaluated, including the expression level of genes characterizing glutamate transmission and neuroinflammation, animal behavior, and hippocampal cell morphology. Significant neuronal cell death occurred in the CA3 and CA4 regions, and to a lesser extent, in the CA1 and CA2 regions. The death of neurons in the CA1 field was significantly reduced in animals with a combined use of memantine and VU 0422288. In the hippocampus of these animals, the level of expression of genes characterizing glutamatergic synaptic transmission (Grin2b, Gria1, EAAT2) did not differ from the level in control animals, as well as the expression of genes characterizing neuroinflammation (IL1b, TGF beta 1, Aif1, and GFAP). However, the expression of genes characterizing neuroinflammation was markedly increased in the hippocampus of animals treated with memantine or VU 0422288 alone after TMT. The results of immunohistochemical studies confirmed a significant activation of microglia in the hippocampus three weeks after TMT injection. In contrast to the hilus, microglia in the CA1 region had an increase in rod-like cells. Moreover, in the CA1 field of the hippocampus of the animals of the MEM + VU group, the amount of such microglia was close to the control. Thus, the short-term modulation of glutamatergic synaptic transmission by memantine and subsequent activation of Group III mGluR significantly affected the dynamics of neurodegeneration in the hippocampus.

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Expression of mGlu Receptor Genes in the Hippocampus After Intoxication with Trimethyltin

et al. 2018

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Effect of Pharmacological Modulation of Activity of Metabotropic Glutamate Receptors on Their Gene Expression after Excitotoxic Damage in Hippocampal Neurons

Cited by 3 publications

References 10 publications

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus

Expression of mGlu Receptor Genes in the Hippocampus After Intoxication with Trimethyltin

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