Age-related changes in nigrostriatal dopaminergic function are accentuated in +/− brain-derived neurotrophic factor mice

Abstract

The effects of a deletion for the brain derived neurotrophic factor (BDNF) allele (± BDNF) upon age-related changes in nigrostriatal dopaminergic (NSDA) function were assessed. Behavioral (beam crossing and spontaneous activity) and neurochemical (potassium-stimulated dopamine release from superfused striatum) measures were compared among Young (4–5 month), Middle (11–13 month) and Aged (19–21 month) ± BDNF and their wild type littermate control (+/+ BDNF) mice. No statistically significant differences were obtained between +/+ and ± BDNF mice at the Young age sampling period for any of the behavioral or neurochemical measures. Behavioral and neurochemical responses indices of NSDA function begin to diverge between +/+ and ± Middle age BDNF mice and maximal differences were observed at the Aged period. For both movement and stereotypy times, scores obtained from +/+ mice were significantly decreased compared with ± BDNF mice at the Aged period and center time scores of +/+ mice were decreased at both the Middle and Aged periods compared with ± BDNF mice. Neurochemically, potassium-stimulated DA release of +/+ mice was significantly greater than ± BDNF mice with maximal differences obtained at the Aged period. These results demonstrate marked differences in age-related changes of NSDA function between +/+ and ± BDNF mice and suggest that the deletion of one allele for BDNF may make these mice more susceptible to age-related declines in NSDA function.