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 crossfrequency coupling specifically characterized the 6-month-old PS2APP mice, just before the surge of the cognitive decline.

Early hippocampal hyperexcitability in PS2APP mice: role of mutant PS2 and APP

FONTANA, ROBERTO;AGOSTINI, MARIO;MURANA, EMANUELE;MAHMUD, MUFTI;SCREMIN, ELENA;RUBEGA, MARIA;SPARACINO, GIOVANNI;VASSANELLI, STEFANO
;
FASOLATO, CRISTINA
2017

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 crossfrequency coupling specifically characterized the 6-month-old PS2APP mice, just before the surge of the cognitive decline.
File in questo prodotto:
File Dimensione Formato  
Accepted manuscript-5-Nov-16.pdf

Open Access dal 19/04/2018

Descrizione: Accepted manuscript Fontana et al.NBA, 2017
Tipologia: Postprint (accepted version)
Licenza: Accesso libero
Dimensione 921.59 kB
Formato Adobe PDF
921.59 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3222145
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 23
  • OpenAlex ND
social impact