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
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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