Expression of mGlu Receptor Genes in the Hippocampus After Intoxication with Trimethyltin
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A variety of localization and signaling properties of eight subtypes of metabotropic glutamate receptors (mGluRs) in the brain provide glutamate an important regulatory role in many processes, including neurodegeneration and repair of neuronal damage. To identify specific subtypes of mGluRs, which are involved in neurodegeneration process, we assessed expression levels of their genes under pathophysiological conditions. Using quantitative real-time RT-PCR analysis, we studied transcription levels of mGlu2-5 and mGlu7 genes in the hippocampus after its damage by neurotoxicant trimethyltin chloride (TMT) in Wistar rats. This organotin compound is known to cause neurodegeneration in the brain, especially in the hippocampus. Morphological studies confirmed neuronal damage in CA3-CA4 subfields of the hippocampus 6 weeks after the treatment with TMT. Step-through passive avoidance test revealed memory deterioration in rat-treated TMT. Interestingly, 3 and 6 weeks after the treatment with TMT, expression levels of the mGlu2 and mGlu7 genes were not changed in comparison to the control values while expression level of mGlu4 genes was upregulated throughout the whole studied period of TMT action. The dynamics of mGlu3 gene expression revealed the existence of neuroinflammation 3 weeks after the treatment with TMT, which was further confirmed by the upregulation of cyclooxygenase-2 gene expression. The expression level of mGlu5 receptors was downregulated 6 weeks after the treatment with TMT. Our results revealed a significant role of mGlu4, mGlu5, and mGlu3 receptors in the neurodegenerative/reparative processes in the hippocampus after the treatment with TMT. Ligands of these receptor subtypes can be, therefore, considered potential therapeutic targets for prevention or reduction of neurodegeneration.
KeywordsTrimethyltin chloride Hippocampus Metabotropic glutamate receptors Gene expression
This work was supported by Russian Foundation for Basic Research (Grant No. 16-34-01167).
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Conflict of Interest
The authors declare that they have no conflicts of interest.
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