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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.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2009 Jul; Vol. 30 (7), pp. 1099-113. Date of Electronic Publication: 2007 Nov 26. - Publication Year :
- 2009
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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.
- Subjects :
- Alzheimer Disease physiopathology
Amyloid beta-Peptides analysis
Amyloid beta-Protein Precursor genetics
Amyloid beta-Protein Precursor metabolism
Animals
Brain pathology
Brain physiopathology
Cannabinoid Receptor Modulators analysis
Cognition Disorders metabolism
Cognition Disorders physiopathology
Cognition Disorders therapy
Disease Models, Animal
Environment, Controlled
Exploratory Behavior physiology
Housing, Animal
Memory, Short-Term physiology
Mice
Mice, Transgenic
Motor Activity physiology
Presenilin-1 genetics
Presenilin-1 metabolism
Stress, Psychological complications
Stress, Psychological metabolism
Stress, Psychological physiopathology
Alzheimer Disease metabolism
Alzheimer Disease therapy
Amyloid beta-Peptides metabolism
Brain metabolism
Cannabinoid Receptor Modulators metabolism
Endocannabinoids
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 30
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 18023506
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2007.10.002