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

Pardon, Marie-Christine and Sarmad, Sarir and Rattray, Ivan and Bates, Timothy E. and Scullion, Gillian A. and Marsden, Charles A. and Barrett, David A. and Lowe, James and Kendall, David A. (2009) 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. Neurobiology of Aging, 30 (7). pp. 1099-1113. ISSN 0197-4580

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Official URL: http://dx.doi.org/10.1016/j.neurobiolaging.2007.10...

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.

Item Type:Article
Keywords:Alzheimer's, TASTPM, amyloid precursor protein, presenilin-1, endocannabinoid
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B140 Neuroscience
B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Science > School of Life Sciences
ID Code:5206
Deposited By: Timothy Bates
Deposited On:26 Jun 2012 06:48
Last Modified:29 Nov 2013 08:43

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