Behavioural Phenotyping of APPswe/PS1δE9 Mice: Age-Rrelated Changes and Effect of Long-Term Paroxetine Treatment.
Alzheimer's disease (AD) is a devastating illness characterized by a progressive loss of cognitive, social, and emotional functions, including memory impairments and more global cognitive deficits. Clinical-epidemiological evidence suggests that neuropsychiatric symptoms precede the onset of cognitive symptoms both in humans with early and late onset AD. The behavioural profile promoted by the AD pathology is believed to associate with degeneration of the serotonergic system. Using the APPswe/PS1δE9 model of AD-like pathology starting with 9 months old mice, we characterised long term non-cognitive behavioural changes measured at 9, 12, 15, and 18 months of age and applied principal component analysis on data obtained from open field, elevated plus maze, and social interaction tests. Long-term treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine was applied to assess the role of 5-HT on the behavioural profile; duration of treatment was 9 months, initiated when mice were 9 months of age. Treatment with paroxetine delays the decline in locomotion, in exploration and risk assessment behaviour, found in the APP/PS1 mice. APP/PS1 mice also exhibit low social activity and less aggressiveness, both of which are not affected by treatment with paroxetine. The APP/PS1 behavioural phenotype, demonstrated in this study, only begins to manifest itself from 12 months of age. Our results indicate that treatment with SSRI might ameliorate some of the behavioural deficits found in aged APP/PS1 mice.
Department of Clinical Medicine, Health, Aarhus University, Risskov, Denmark.
Louise Ørum
LØ
Olesen
Department of Clinical Medicine, Health, Aarhus University, Risskov, Denmark.
Elena V
EV
Bouzinova
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
Maurizio
M
Severino
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
Mithula
M
Sivasaravanaparan
Department of Forensic Medicine, Health, Aarhus University, Aarhus N, Denmark.
Jørgen Bo
JB
Hasselstrøm
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
Bente
B
Finsen
Department of Clinical Medicine, Health, Aarhus University, Risskov, Denmark.
Ove
O
Wiborg
D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017374:Paroxetine / Q000008:administration & dosage*; D053764:Presenilin-1 / Q000378:metabolism*; D012919:Social Behavior
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D017374:Paroxetine