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

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

Dluzen D E; McDermott J L; Anderson L I; Kucera J; Joyce J N; Osredkar T; Walro J M

Neuroscience

2004

1905-06

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.

*Aging; Animals; Brain-Derived Neurotrophic Factor/*genetics/*metabolism; Corpus Striatum/*metabolism; Dopamine/*biosynthesis; Mice; Motor Activity/physiology; Mutant Strains; Mutation; Substantia Nigra/*metabolism

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