title: Sex-dependent alterations in social behaviour and cortical synaptic activity coincide at different ages in a model of Alzheimer's disease.
abstract: Besides memory deficits, Alzheimer's disease (AD) patients suffer from neuropsychiatric symptoms, including alterations in social interactions, which are subject of a growing number of investigations in transgenic models of AD. Yet the biological mechanisms underlying these behavioural alterations are poorly understood. Here, a social interaction paradigm was used to assess social dysfunction in the triple-transgenic mouse model of AD (3xTg-AD). We observed that transgenic mice displayed dimorphic behavioural abnormalities at different ages. Social disinhibition was observed in 18 months old 3xTg-AD males compared to age and sex-matched control mice. In 3xTg-AD females, social disinhibition was present at 12 months followed by reduced social interactions at 18 months. These dimorphic behavioural alterations were not associated with alterations in AD neuropathological markers such as Aβ or tau levels in the frontal cortex. However, patch-clamp recordings revealed that enhanced social interactions coincided temporally with an increase in both excitatory and inhibitory basal synaptic inputs to layer 2-3 pyramidal neurons in the prefrontal cortex. These findings uncover a novel pattern of occurrence of psychiatric-like symptoms between sexes in an AD model. Our results also reveal that functional alterations in synapse activity appear as a potentially significant substrate underlying behavioural correlates of AD.
authors.affiliation: Faculty of Medicine Laval University, Quebec City, Quebec, Canada.
authors.forename: Cyril
authors.initials: C
authors.lastname: Bories
authors.forename: Matthieu J
authors.initials: MJ
authors.lastname: Guitton
authors.forename: Carl
authors.initials: C
authors.lastname: Julien
authors.forename: Cyntia
authors.initials: C
authors.lastname: Tremblay
authors.forename: Milène
authors.initials: M
authors.lastname: Vandal
authors.forename: Meriem
authors.initials: M
authors.lastname: Msaid
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012737:Sex Factors; D012919:Social Behavior; D013569:Synapses / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins