Sex-Dependent Alterations in Social Behaviour and Cortical Synaptic Activity Coincide at Different Ages in a Model of Alzheimer's Disease

被引:52
|
作者
Bories, Cyril [2 ,4 ]
Guitton, Matthieu J. [1 ,2 ,4 ]
Julien, Carl [1 ,3 ]
Tremblay, Cyntia [1 ,3 ]
Vandal, Milene [1 ,3 ]
Msaid, Meriem [1 ,3 ]
De Koninck, Yves [2 ,4 ]
Calon, Frederic [1 ,3 ]
机构
[1] Univ Laval, Fac Pharm, Quebec City, PQ, Canada
[2] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada
[3] CHU Laval, Res Ctr, Quebec City, PQ G1V 4G2, Canada
[4] Quebec Mental Hlth Inst, Quebec City, PQ, Canada
来源
PLOS ONE | 2012年 / 7卷 / 09期
基金
加拿大创新基金会; 加拿大健康研究院;
关键词
DEVELOPMENTAL-GENETIC ANALYSIS; MEDIAL PREFRONTAL CORTEX; MILD COGNITIVE IMPAIRMENT; APPSWE/PS1 BIGENIC MODEL; TRANSGENIC MOUSE MODEL; A-BETA; AGGRESSIVE-BEHAVIOR; NEUROPSYCHIATRIC SYMPTOMS; MICE; APATHY;
D O I
10.1371/journal.pone.0046111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 A beta 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.
引用
收藏
页数:8
相关论文
共 50 条
  • [31] Sex-Dependent Changes in Body Composition and Bone Mineral Density in Wild Type Mice and the APP-SAA Alzheimer's Disease Mouse Model
    Ramirez, Gabriel
    Teal, Alix
    Chellaganapathy, Lakshmi
    Pianeta, Roquelina
    Essex, Alyson
    Yamada, Chiaki
    Movila, Alexandru
    Plotkin, Lilian I.
    JOURNAL OF BONE AND MINERAL RESEARCH, 2024, 39 : 274 - 274
  • [32] Age-dependent alterations in the presynaptic active zone in a Drosophila model of Alzheimer's Disease
    Huang, Jian-Kang
    Ma, Ping-Li
    Ji, Su-Ying
    Zhao, Xiao-Liang
    Tan, Jiang-Xiu
    Sun, Xiao-Jiang
    Huang, Fu-De
    NEUROBIOLOGY OF DISEASE, 2013, 51 : 161 - 167
  • [33] Akt activation ameliorates deficits in hippocampal-dependent memory and activity-dependent synaptic protein synthesis in an Alzheimer's disease mouse model
    Kommaddi, Reddy Peera
    Gowaikar, Ruturaj
    Haseena, P. A.
    Diwakar, Latha
    Singh, Kunal
    Mondal, Amrita
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2024, 300 (02)
  • [34] Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer's disease
    Baglietto-Vargas, David
    Prieto, Gilberto Aleph
    Limon, Agenor
    Forner, Stefania
    Rodriguez-Ortiz, Carlos J.
    Ikemura, Kenji
    Ager, Rahasson R.
    Medeiros, Rodrigo
    Trujillo-Estrada, Laura
    Martini, Alessandra C.
    Kitazawa, Masashi
    Davila, Jose C.
    Cotman, Carl W.
    Gutierrez, Antonia
    LaFerla, Frank M.
    AGING CELL, 2018, 17 (04)
  • [35] Bioactive Food Abates Metabolic and Synaptic Alterations by Modulation of Gut Microbiota in a Mouse Model of Alzheimer's Disease
    Syeda, Tauqeerunnisa
    Sanchez-Tapia, Monica
    Pinedo-Vargas, Laura
    Granados, Omar
    Cuervo-Zanatta, Daniel
    Rojas-Santiago, Eleazar
    Diaz-Cintra, Sofia
    Torres, Nimbe
    Perez-Cruz, Claudia
    JOURNAL OF ALZHEIMERS DISEASE, 2018, 66 (04) : 1657 - 1682
  • [36] Infiltrating Hematogenous Macrophages Aggregate Around β-Amyloid Plaques in an Age- and Sex-Dependent Manner in a Mouse Model of Alzheimer Disease
    Kozyrev, Natalie
    Albers, Shawn
    Yang, Jennifer
    Prado, Vania F.
    Prado, Marco A. M.
    Fonseca, Gregory J.
    Rylett, R. Jane
    Dekaban, Gregory A.
    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2020, 79 (11): : 1147 - 1162
  • [37] 5xFAD Mice Display Sex-Dependent Inflammatory Gene Induction During the Prodromal Stage of Alzheimer's Disease
    Manji, Zahra
    Rojas, Asheebo
    Wang, Wenyi
    Dingledine, Raymond
    Varvel, Nicholas H.
    Ganesh, Thota
    JOURNAL OF ALZHEIMERS DISEASE, 2019, 70 (04) : 1259 - 1274
  • [38] Alterations in Odor Hedonics in the 5XFAD Alzheimer's Disease Mouse Model and the Influence of Sex
    Roberts, Elizabeth R.
    Dossat, Amanda M.
    Cortijo, Maria del Mar
    Brundin, Patrik
    Wesson, Daniel W.
    BEHAVIORAL NEUROSCIENCE, 2020, 134 (05) : 407 - 416
  • [39] NLRP3-dependent synaptic plasticity deficit in an Alzheimer's disease amyloidosis model in vivo
    Qi, Yingjie
    Klyubin, Igor
    Cuello, A. Claudio
    Rowan, Michael J.
    NEUROBIOLOGY OF DISEASE, 2018, 114 : 24 - 30
  • [40] Monosynaptic Rabies Tracing Reveals Sex- and Age-Dependent Dorsal Subiculum Connectivity Alterations in an Alzheimer's Disease Mouse Model
    Ye, Qiao
    Gast, Gocylen
    Wilfley, Erik George
    Huynh, Hanh
    Hays, Chelsea
    Holmes, Todd C.
    Xu, Xiangmin
    JOURNAL OF NEUROSCIENCE, 2024, 44 (16):