Brain-derived neurotrophic factor (BDNF) is a protein that plays an important role in neuronal survival, differentiation, and synaptic plasticity. Alterations in BDNF have been found to contribute to anxiety-related behaviors and to differences in performance in learning and memory tasks. Mice with constitutive reductions in BDNF are characterized as being hyperphagic, hyperlocomotive or hypolocomotive, and impaired in high stress spatial memory paradigms (i.e., Morris water maze). However, there are many conflicting reports of these characteristics and several investigators have been unable to detect differences in spatial memory performance or anxiety-like behavior, particularly in aging animals.
In addition, there is little agreement on changes in activity levels of BDNF-deficient mice. In the present study, we assessed the performance of a large cohort of mixed sex mice with constitutive reductions in BDNF (25 months of age; n=50) in the elevated plus maze, open field, and the Lashley III maze, a low stress learning and memory test, to evaluate the effects of aging on behaviors thought to be influenced by BDNF. No significant differences were found between
BDNF +/+ and BDNF +/- mice in the elevated plus maze, suggesting the absence of an increased anxiety-related phenotype in these mice at an older age. In the open field, there were no differences in total distance traveled or other measures of horizontal and vertical movement. The most striking findings were in the Lashley III maze. This is a routelearning task that does not rely on aversive stimuli or visual cues. Highly significant main effects of genotype were observed in the number of errors (p<0.001), days to criterion (p<0.001), and learning index (p<0.001), with BDNF +/- mice of both sexes performing better than age-matched BDNF +/+ mice on each of these parameters. These data imply that the effects of constitutive reductions in BDNF vary with respect to age. Furthermore, they suggest that learning behaviors under different levels of stress (i.e. swimming, foot shock) may result in qualitatively different outcomes in behavior testing paradigms.