Differential proteomic and behavioral effects of long-term XXXX in wild-type and APP-overexpressing transgenics.

@entity20933 @entity19 @entity73 @entity195 @entity2798
Physical exercise may provide protection against the @entity73 associated with @entity195 , although the mechanisms are not clear. In the present study, APP/ @entity20933 double-transgenic and wild-type @entity19 were allowed unlimited @entity2798 for 7months. Consistent with previous reports, wheel-running improved cognition in the double- @entity19 . Interestingly, the average daily distance run was strongly correlated with spatial memory in the water maze in wild-type @entity19 (r(2)=.959), but uncorrelated in transgenics (r(2)=.013). Proteomics analysis showed that sedentary @entity19 differed significantly from sedentary wild-types with respect to proteins involved in synaptic transmission, cytoskeletal regulation, and neurogenesis. When given an opportunity to exercise, the transgenics' deficiencies in cytoskeletal regulation and neurogenesis largely normalized, but abnormal synaptic proteins did not change. In contrast, exercise enhanced proteins associated with cytoskeletal regulation, oxidative phosphorylation, and synaptic transmission in wild-type @entity19 . Soluble and insoluble Ab40 and Ab42 levels were significantly decreased in both cortex and hippocampus of active transgenics, suggesting that this may have played a role in the cognitive improvement in APP/ @entity20933 @entity19 . b-secretase was significantly reduced in active APP/ @entity20933 @entity19 compared to sedentary controls, suggesting a mechanism for reduced Ab. Taken together, these data illustrate that exercise improves memory in wild-type and APP-overexpressing @entity19 in fundamentally different ways.
