title: Novel cage stress alters remote contextual fear extinction and regional T2 magnetic resonance relaxation times in TASTPM mice overexpressing amyloid.
abstract: We have previously shown that repeated exposure to mild novel cage stress prevents the onset of recent contextual fear memory deficits and attenuated amyloid deposition in the TASTPM mouse model of Alzheimer's disease. Here, we extended this investigation to remote contextual fear memory and extinction. TASTPM and wild-type mice acquired contextual fear at 4 months of age. Retention and extinction of contextual fear were assessed at 5.5 months prior to in vivo MRI assessment of regional T2 relaxation times and brain volumes followed by immunostaining to determine amyloid plaque load. Remote contextual fear memory was preserved in TASTPM mice regardless of the stress condition. Stress impaired extinction in wild-type mice but facilitated this process in TASTPM mice. Genotype-dependent effects of stress were observed on regional T2 times which were prolonged in the subiculum and thalamus of stressed TASTPM, possibly reflecting reduced amyloid pathology. Amyloid plaque load was particularly decreased in the retrosplenial cortex of stressed TASTPM mice, which also showed an overall reduction in the number of diffuse plaques. These findings support the hypothesis that repeated mild levels of stress induced by novel activities can delay the progression of pathological changes relevant to Alzheimer's disease.
authors.affiliation: School of Biomedical Sciences, Academic Radiology, Queen's Medical Centre, Nottingham, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rattray
authors.forename: Alain
authors.initials: A
authors.lastname: Pitiot
authors.forename: James
authors.initials: J
authors.lastname: Lowe
authors.forename: Dorothee P
authors.initials: DP
authors.lastname: Auer
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Lima
authors.forename: Mirjam I
authors.initials: MI
authors.lastname: Schubert
authors.forename: Malcolm J W
authors.initials: MJ
authors.lastname: Prior
authors.forename: Charles A
authors.initials: CA
authors.lastname: Marsden
authors.forename: Fernando Pérez
authors.initials: FP
authors.lastname: Diaz
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Pardon
mesh_terms: D000682:Amyloid / Q000096:biosynthesis / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004192:Discrimination, Psychological / Q000502:physiology; D004597:Electroshock; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000523:psychology*; D005838:Genotype; D006799:Housing, Animal; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011597:Psychomotor Performance; D013028:Space Perception / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018076:DNA, Complementary