| Reference : mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment of Absence Epile... |
| Scientific journals : Article | |||
| Life sciences : Genetics & genetic processes Human health sciences : Neurology | |||
| Systems Biomedicine | |||
| http://hdl.handle.net/10993/51870 | |||
| mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment of Absence Epilepsy: Preclinical and Human Genetics Data | |
| English | |
| Celli, Roberta [] | |
| Striano, Pasquale [] | |
| Citraro, Rita [] | |
| Di Menna, Luisa [] | |
| Cannella, Milena [] | |
| Imbriglio, Tiziana [] | |
| Koko, Mahmoud [] | |
| Consortium, EuroEPINOMICS-CoGIE [] | |
May, Patrick  [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core >] | |
| Krause, Roland [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core >] | |
| De Sarro, Giovambattista [] | |
| Monn, James A. [] | |
| Battaglia, Giuseppe [] | |
| van Luitjelaar, Gilles [] | |
| Nicoletti, Ferdinando [] | |
| Russo, Emilio [] | |
| Leo, Antonio [] | |
| 9-May-2022 | |
| Current Neuropharmacology | |
| Bentham Science Publishers | |
| Yes | |
| International | |
| 1570-159X | |
| United Arab Emirates | |
| [en] Absence epilepsy ; mGlu3 receptors ; cortico-thalamo-cortical network ; EEG ; GABA ; glutamate ; human genetics | |
| [en] Abstract: Background: Previous studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for treating absence epilepsy. However, no information is
available on mGlu3 receptors. Objective: To examine whether (i) changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spike- wave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy. Methods: Animals: immunoblot analysis of mGlu3 receptors, GAT-1, GLAST, and GLT-1; real- time PCR analysis of mGlu3 mRNA levels; assessment of mGlu3 receptor signaling; EEG analysis of SWDs; assessment of depressive-like behavior. Humans: search for GRM3 and GRM5 missense variants in 196 patients with absence epilepsy or other Idiopathic Generalized Epilepsy (IGE)/ Genetic Generalized Epilepsy (GGE) and 125,748 controls. Results: mGlu3 protein levels and mGlu3-mediated inhibition of cAMP formation were reduced in the thalamus and somatosensory cortex of pre-symptomatic (25-27 days old) and symptomatic (6-7 months old) WAG/Rij rats compared to age-matched controls. Treatment with LY2794193 (1 or 10 mg/kg, i.p.) reduced absence seizures and depressive-like behavior in WAG/Rij rats. LY2794193 also enhanced GAT1, GLAST, and GLT-1 protein levels in the thalamus and somatosensory cortex. GRM3 and GRM5 gene variants did not differ between epileptic patients and controls. Conclusion: We suggest that mGlu3 receptors modulate the activity of the cortico-thalamo-cortical circuit underlying SWDs and that selective mGlu3 receptor agonists are promising candidate drugs for absence epilepsy treatment. | |
| Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) | |
| Researchers ; Professionals ; Students | |
| http://hdl.handle.net/10993/51870 | |
| 10.2174/1570159X20666220509160511 | |
| https://www.eurekaselect.com/article/123246 |
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