The mGlu7 receptor provides protective effects against epileptogenesis and epileptic seizures
Autor: | Tristan Bouschet, Benoit Girard, Laurent Fagni, Maria Paula Moreno, Julien Dairou, Julie Perroy, Francine Acher, Annie Varrault, Pola Tuduri, Jihane Vitre, Sophie Sakkaki, Nicola Marchi, Isabelle McCort-Tranchepain, Federica Bertaso, Cedric Barboux |
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Přispěvatelé: | Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Agonist Kainic acid medicine.drug_class [SDV]Life Sciences [q-bio] [CHIM.THER]Chemical Sciences/Medicinal Chemistry Receptors Metabotropic Glutamate Hippocampus Epileptogenesis lcsh:RC321-571 Epilepsy Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neuropharmacology Seizures Excitatory Amino Acid Agonists Kindling Neurologic medicine Animals Pentylenetetrazol Receptor lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry 030304 developmental biology 0303 health sciences Hippocampal sclerosis business.industry Kindling [CHIM.ORGA]Chemical Sciences/Organic chemistry Aminobutyrates Metabotropic glutamate receptor medicine.disease Mice Mutant Strains Animal models 030104 developmental biology Neurology chemistry Anticonvulsants business Neuroscience 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Neurobiology of Disease Neurobiology of Disease, Elsevier, 2019, 129, pp.13-28. ⟨10.1016/j.nbd.2019.04.016⟩ Neurobiology of Disease, Vol 129, Iss, Pp 13-28 (2019) |
ISSN: | 0969-9961 1095-953X |
Popis: | Finding new targets to control or reduce seizure activity is essential to improve the management of epileptic patients. We hypothesized that activation of the pre-synaptic and inhibitory metabotropic glutamate receptor type 7 (mGlu7) reduces spontaneous seizures.We tested LSP2-9166, a recently developed mGlu7/4 agonist with unprecedented potency on mGlu7 receptors, in two paradigms of epileptogenesis. In a model of chemically induced epileptogenesis (pentylenetetrazol systemic injection), LSP2-9166 induces an anti-epileptogenic effect rarely observed in preclinical studies. In particular, we found a bidirectional modulation of seizure progression by mGlu4 and mGlu7 receptors, the latter preventing kindling. In the intra-hippocampal injection of kainic acid mouse model that mimics the human mesial temporal lobe epilepsy, we found LSP2-9166 reduced seizure frequency and hippocampal sclerosis. LSP2-9166 also acts as an anti-epileptic drug on established seizures in both models tested.Specific modulation of the mGlu7 receptor could represent a novel approach to reduce pathological network remodeling. |
Databáze: | OpenAIRE |
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