title: Early onset of hypersynchronous network activity and expression of a marker of chronic seizures in the Tg2576 mouse model of Alzheimer's disease.
abstract: Cortical and hippocampal hypersynchrony of neuronal networks seems to be an early event in Alzheimer's disease pathogenesis. Many mouse models of the disease also present neuronal network hypersynchrony, as evidenced by higher susceptibility to pharmacologically-induced seizures, electroencephalographic seizures accompanied by spontaneous interictal spikes and expression of markers of chronic seizures such as neuropeptide Y ectopic expression in mossy fibers. This network hypersynchrony is thought to contribute to memory deficits, but whether it precedes the onset of memory deficits or not in mouse models remains unknown. The earliest memory impairments in the Tg2576 mouse model of Alzheimer's disease have been observed at 3 months of age. We thus assessed network hypersynchrony in Tg2576 and non-transgenic male mice at 1.5, 3 and 6 months of age. As soon as 1.5 months of age, Tg2576 mice presented higher seizure susceptibility to systemic injection of a GABAA receptor antagonist. They also displayed spontaneous interictal spikes on EEG recordings. Some Tg2576 mice presented hippocampal ectopic expression of neuropeptide Y which incidence seems to increase with age among the Tg2576 population. Our data reveal that network hypersynchrony appears very early in Tg2576 mice, before any demonstrated memory impairments.
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bezzina
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Verret
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Juan
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Remaud
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Halley
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Rampon
authors.affiliation: Université de Toulouse; UPS; Centre de Recherches sur la Cognition Animale; 118 route de Narbonne, F-31062, Toulouse, Cedex 09, France; CNRS, Centre de Recherches sur la Cognition Animale, F-31062, Toulouse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Dahan
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004569:Electroencephalography; D058407:Electroencephalography Phase Synchronization / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000378:metabolism; D012640:Seizures / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D058787:GABA-A Receptor Antagonists; D009478:Neuropeptide Y