MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy
Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases....
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2022-01-01
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| author | Alexandra V. Dyomina Anna A. Kovalenko Maria V. Zakharova Tatiana Yu. Postnikova Alexandra V. Griflyuk Ilya V. Smolensky Irina V. Antonova Aleksey V. Zaitsev |
| author_facet | Alexandra V. Dyomina Anna A. Kovalenko Maria V. Zakharova Tatiana Yu. Postnikova Alexandra V. Griflyuk Ilya V. Smolensky Irina V. Antonova Aleksey V. Zaitsev |
| author_sort | Alexandra V. Dyomina |
| collection | DOAJ |
| description | Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:37:28Z |
| publishDate | 2022-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4aa412eaaa684392945c43cb442c2dab2023-11-23T11:40:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123149710.3390/ijms23010497MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of EpilepsyAlexandra V. Dyomina0Anna A. Kovalenko1Maria V. Zakharova2Tatiana Yu. Postnikova3Alexandra V. Griflyuk4Ilya V. Smolensky5Irina V. Antonova6Aleksey V. Zaitsev7Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 194223 Saint Petersburg, RussiaMetabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.https://www.mdpi.com/1422-0067/23/1/497temporal lobe epilepsyexcitatory amino acid transporter 2glial fibrillary acidic proteinopen field testnovel object recognition testhippocampus |
| spellingShingle | Alexandra V. Dyomina Anna A. Kovalenko Maria V. Zakharova Tatiana Yu. Postnikova Alexandra V. Griflyuk Ilya V. Smolensky Irina V. Antonova Aleksey V. Zaitsev MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy International Journal of Molecular Sciences temporal lobe epilepsy excitatory amino acid transporter 2 glial fibrillary acidic protein open field test novel object recognition test hippocampus |
| title | MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy |
| title_full | MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy |
| title_fullStr | MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy |
| title_full_unstemmed | MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy |
| title_short | MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy |
| title_sort | mtep a selective mglur5 antagonist had a neuroprotective effect but did not prevent the development of spontaneous recurrent seizures and behavioral comorbidities in the rat lithium pilocarpine model of epilepsy |
| topic | temporal lobe epilepsy excitatory amino acid transporter 2 glial fibrillary acidic protein open field test novel object recognition test hippocampus |
| url | https://www.mdpi.com/1422-0067/23/1/497 |
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