Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice.
We sought to determine if sex impacts the cognitive and neuropathological phenotype of the 3xTg-AD mice. We find that male and female 3xTg-AD mice show comparable impairments on Morris water maze (MWM) and inhibitory avoidance (IA) at 4 months. Shortly thereafter, however, the cognitive performance varies among the sexes, with females performing worse than males. These behavioral differences are not attributable to differences in Abeta or tau levels. The behavioral effect is transient as from 12 months onward, the disparity is no longer apparent. Because females perform worse than males on stressful tasks, we explored their corticosterone responses and find that young female 3xTg-AD mice show markedly heightened corticosterone response after 5 days of MWM training compared to age-matched male 3xTg-AD mice; this difference is no longer apparent in older mice. Thus, the enhanced corticosterone response of the young female mice likely underlies their poorer performance on stressful tasks.
Department of Neurobiology and Behavior, 1109 Gillespie Neuroscience Research Facility, University of California, Irvine, Irvine, CA 92697-4545, USA.
Lani K
LK
Clinton
Lauren M
LM
Billings
Kim N
KN
Green
Antonella
A
Caccamo
Jerry
J
Ngo
Salvatore
S
Oddo
James L
JL
McGaugh
Frank M
FM
LaFerla
D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology; D003345:Corticosterone / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology
D016229:Amyloid beta-Peptides; D003345:Corticosterone