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

• Published in: Neurobiology of aging Vol. 30; no. 7; pp. 1099 - 1113
• Main Authors: Pardon, Marie-Christine, Sarmad, Sarir, Rattray, Ivan, Bates, Timothy E, Scullion, Gillian A, Marsden, Charles A, Barrett, David A, Lowe, James, Kendall, David A
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.07.2009; Elsevier
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; Biological and medical sciences; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brain endocannabinoids; Cannabinoid Receptor Modulators - analysis; Cannabinoid Receptor Modulators - metabolism; Cognition Disorders - metabolism; Cognition Disorders - physiopathology; Cognition Disorders - therapy; Contextual fear conditioning; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; Endocannabinoids; Environment, Controlled; Environmental enrichment; Exploratory Behavior - physiology; Fundamental and applied biological sciences. Psychology; Housing, Animal; Internal Medicine; Medical sciences; Memory, Short-Term - physiology; Mice; Mice, Transgenic; Motor Activity - physiology; Neurology; Presenilin-1 - genetics; Presenilin-1 - metabolism; Psychological stress; Stress, Psychological - complications; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Transgenic mice; Vertebrates: nervous system and sense organs; Psychological stress; Environmental enrichment; Transgenic mice; Contextual fear conditioning; Brain endocannabinoids; Amyloid; Alzheimer's disease; Senescence; Alzheimer disease; Central nervous system; Transgenic animal; Cognition; Cannabinoid; Stimulating environment; Encephalon; Endocannabinoid; Degenerative disease; Conditioning; Nervous system diseases; Rodentia; Stress; Cerebral disorder; Fear; Vertebrata; Mammalia; Mouse; Central nervous system disease; Early
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.10.002

Abstract 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.