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P4‐041: Voluntary exercise ameliorates both cognitive and noncognitive symptoms in the 3xTgAD mouse

2009; Wiley; Volume: 5; Issue: 4S_Part_15 Linguagem: Inglês

10.1016/j.jalz.2009.04.911

1552-5279

Yoelvis García, Susana Revilla, Rosa Cristòfol, Crsistina Suñol, Frank M. LaFerla, Lydia Giménez‐Llort, Coral Sanfeliu,

Tryptophan and brain disorders

The beneficial effects of regular physical exercise in older patients with depression and other mood disorders are well known. Similarly, a number of studies suggest that fitness enhances cognition in humans. Therefore, participation in a regular exercise program is increasingly proposed as an intervention that could prevent or reduce cognitive and mood disorders of age-associated dementias, mainly Alzheimer's disease (AD). In this work we analyzed the effects of voluntary exercise in triple transgenic 3xTgAD mouse model for AD, on both cognitive and behavioral psychiatric symptoms of dementia (BPSD) and the underlying neuronal changes. Male and female 3xTgAD and wild type mice had free access to an activity wheel. Mice of 4 months had been submitted to one month of exercise; mice of 7 months had been submitted to one or six months of exercise. Then, sensorimotor abilities, BPSD-like behaviors and learning and memory were tested. Brain amyloid beta was determined by ELISA and immunohistochemistry. Levels of glutathione and antioxidant enzymes were quantified spectrophotometrically in cerebral cortex. Binding of flunitrazepam to GABAA receptor was analyzed through radiometric binding methods in cerebral cortex. We analyzed the effects of voluntary exercise at early stages of AD (4 and 7 month old 3xTgAD mice). As expected, AD neuropathological traits were more significant at 7 than at 4 months. Main behavioral alterations were higher anxiety and lesser cognitive capacity. In general, exercise ameliorated neuropathological behaviors, increased antioxidant defense, and showed a tendency to ameliorate GABAA receptor functionality. Neuroprotection after six months of exercise was stronger than after one month, and totally prevented anxiety-related behaviors. Voluntary exercise showed a neuroprotective effect at the early stages of AD of 3xTgAD mice, including both cognitive and BPSD-like behaviors. More work is ongoing to clarify the mechanisms involved. This work provides more evidence to demonstrate the validity of voluntary exercise as a promising coadyuvant therapy to prevent or ameliorate AD symptoms and its relevance to be included in our life style. (This work was supported by grants 062931 from Fundació La Marató de TV3 and RD06/0913/1004 from ISCIII, Spain).