Titre :

The reduction in glutamate release is predictive of cognitive and emotional alterations that are corrected by the positive modulator of AMPA receptors S 47445 in perinatal stressed rats

Auteur(s) :

Morley-Fletcher, Sara [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Zuena, A. R. [Auteur]

Mairesse, Jérôme [Auteur]
Université de Genève = University of Geneva [UNIGE]
Gatta, E. [Auteur]
University of Illinois [Chicago] [UIC]
Van Camp, Gilles [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bouwalerh, Hammou [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Riozzi, Barbara [Auteur]
Istituto Neurologico Mediterraneo [NEUROMED I.R.C.C.S.]
Battaglia, Giuseppe [Auteur]
Istituto Neurologico Mediterraneo [NEUROMED I.R.C.C.S.]
Pittaluga, Anna [Auteur]
Université de Genève = University of Geneva [UNIGE]
Olivero, Guendalina [Auteur]
Université de Genève = University of Geneva [UNIGE]
Mocaer, E. [Auteur]
Institut de Recherches SERVIER [IRS]
Bretin, S. [Auteur]
Institut de Recherches SERVIER [IRS]
Nicoletti, F. [Auteur]

Istituto Neurologico Mediterraneo [NEUROMED I.R.C.C.S.]
Maccari, Stefania [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Titre de la revue :

Neuropharmacology

Nom court de la revue :

Neuropharmacology

Numéro :

135

Pagination :

284-296

Date de publication :

2018-06

ISSN :

1873-7064

Mot(s)-clé(s) en anglais :

AMPAR-PAMs
Early life programming
Glutamate transmission
Predictive validity
Preclinical model
Stress-related disorders

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Pédiatrie

Résumé en anglais : [en]

S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive and anti-stress properties. Here, the drug was assessed in the ...
Lire la suite >S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive and anti-stress properties. Here, the drug was assessed in the perinatal stress (PRS) rat model, known to have a high predictive validity with monoaminergic antidepressants. The effects of a chronic treatment (i.p.) with S 47445 were investigated on risk-taking, motivational and cognitive behavior. S 47445 (1 and 10 mg/kg) increased the exploration of the elevated-plus maze and light/dark box as well as the time spent grooming in the splash test, and improved social memory in PRS rats. Also, the effects of S 47445 were examined on the synaptic neurotransmission. The reduced depolarization-evoked glutamate release induced by PRS was corrected with S 47445 (10 mg/kg). Remarkably, the reduction in glutamate release induced by PRS and corrected by S 47445 chronic treatment was correlated with all the behavioral changes. S 47445 at 10 mg/kg also normalized the lower levels of synaptic vesicle-associated proteins in ventral hippocampus in PRS rats. Finally, S 47445 reversed the decrease of mGlu5 receptors, GR and OXTR induced by PRS. Collectively, in an animal model of stress-related disorders, S 47445 corrected the imbalance between excitatory and inhibitory neurotransmission by regulating glutamate-evoked release that is predictive of PRS behavioral alterations, and also normalized the reduction of trafficking of synaptic vesicles induced by PRS. These results support the interest of glutamatergic-based therapeutic strategies to alleviate stress-related disorders.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Glycostress

Date de dépôt :

2020-02-12T15:11:40Z
2021-03-03T09:52:24Z