title: Early hippocampal hyperexcitability in PS2APP mice: role of mutant PS2 and APP.
abstract: Alterations of brain network activity are observable in Alzheimer's disease (AD) together with the occurrence of mild cognitive impairment, before overt pathology. However, in humans as well in AD mouse models, identification of early biomarkers of network dysfunction is still at its beginning. We performed in vivo recordings of local field potential activity in the dentate gyrus of PS2APP mice expressing the human amyloid precursor protein (APP) Swedish mutation and the presenilin-2 (PS2) N141I. From a frequency-domain analysis, we uncovered network hyper-synchronicity as early as 3 months, when intracellular accumulation of amyloid beta was also observable. In addition, at 6 months of age, we identified network hyperactivity in the beta/gamma frequency bands, along with increased theta-beta and theta-gamma phase-amplitude cross-frequency coupling, in coincidence with the histopathological traits of the disease. Although hyperactivity and hypersynchronicity were respectively detected in mice expressing the PS2-N141I or the APP Swedish mutant alone, the increase in cross-frequency coupling specifically characterized the 6-month-old PS2APP mice, just before the surge of the cognitive decline.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fontana
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Murana
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Mufti
authors.initials: M
authors.lastname: Mahmud
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Scremin
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Rubega
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sparacino
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy. Electronic address: stefano.vassanelli@unipd.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vassanelli
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy. Electronic address: cristina.fasolato@unipd.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fasolato
mesh_terms: D000200:Action Potentials; D000544:Alzheimer Disease / Q000503:physiopathology* / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003071:Cognition; D060825:Cognitive Dysfunction / Q000503:physiopathology; D018891:Dentate Gyrus / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D053766:Presenilin-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053766:Presenilin-2
keywords: Alzheimer's disease; Amyloid beta; Dentate gyrus; Hyperexcitability; Local field potential; PS2APP