Repeated novel cage exposure-induced improvement of early Alzheimer's-like cognitive and amyloid changes in TASTPM mice is unrelated to changes in brain endocannabinoids levels.
Environmental factors (e.g. stress, exercise, enrichment) are thought to play a role in the development of Alzheimer's disease later in life. We investigated the influence of repeated novel cage exposure on the development of early Alzheimer's-like pathology in adult (4 months old) double transgenic mice over-expressing the amyloid precursor protein and presenilin-1 genes (TASTPM mouse line). The procedure involves the repeated placement of the animal into a novel clean cage, a manipulation which induces a stress response and exploratory activity and, as such, can also be seen as a mild form of enrichment. Before and after exposure to the novel cage procedure, separate groups of mice were evaluated for locomotor performance and short-term contextual memory in the fear-conditioning test. Repeated novel cage exposure prevented the onset of a short-term memory deficit that was apparent in 5.5- but not 4-month-old TASTPM mice, without reversing the deficit in extinction already evident at 4 months of age. Brain regional levels of soluble and insoluble amyloid and of endocannabinoids were quantified. Novel cage exposure attenuated soluble and insoluble amyloid accumulation in the hippocampus and frontal cortex, without affecting the age-related increases in regional brain endocannabinoids levels. These beneficial effects are likely to be the consequence of the increase in physical and exploratory activity induced by novel cage exposure and suggest that the impact of environmental factors on Alzheimer's-like changes may be dependent on the degree of activation of stress pathways.
Pardon
Marie-Christine
MC
University of Nottingham Medical School, Institute of Neuroscience, School of Biomedical Sciences, Queen's Medical Centre, Nottingham, United Kingdom. marie.pardon@nottingham.ac.uk
Sarmad
Sarir
S
Rattray
Ivan
I
Bates
Timothy E
TE
Scullion
Gillian A
GA
Marsden
Charles A
CA
Barrett
David A
DA
Lowe
James
J
Kendall
David A
DA
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D063385:Cannabinoid Receptor Modulators / Q000032:analysis / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D063388:Endocannabinoids; D004780:Environment, Controlled; D005106:Exploratory Behavior / Q000502:physiology; D006799:Housing, Animal; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053764:Presenilin-1