GDNF improves cerebellar Purkinje neuron function in aged F344 rats

P. C. Bickford, K. Bowenkamp, G. Taglialatela, G. Hoertig, A. C. Granholm

    Research output: Contribution to journalArticlepeer-review

    4 Scopus citations

    Abstract

    Aging is associated with a decline in the function of β-adrenergic receptor responses in the cerebellum. This decline in noradrenergic receptor sensitivity may underlie some of the accompanying age-related declines in motoric learning behaviors. Glial cell line-derived neurotrophic factor (GDNF) has been reported to prevent the degeneration of noradrenergic neurons following neurotoxic lesions. Thus, it was of interest to examine if GDNF would have a beneficial effect on age-related declines in noradrenergic function. Eighteen-month-old F344 rats were injected with 500 μg GDNF in 20 μl into the cisterna magna. Three weeks following GDNF or vehicle treatment, rats were tested on a motor coordination task and then examined electrophysiologically under urethane anesthesia. GDNF did not produce an improvement in performance on an inclined balance beam or an accelerating rotorod. In young (3-month-old) F344 rats isoproterenol (ISO) will increase GABAergic inhibitions in the majority of cells examined; however, in aged rats only about 30% of neurons demonstrate this phenotype. In the aged rats treated with GDNF, ISO was able to increase GABAergic inhibitions in greater than 75% of the neurons tested, thus returning the neurons to a young phenotype. We examined the brains for expression of bcl-2, which has been shown to be increased in the aged cerebellum. GDNF was able to down-regulate this neuronal signal. Thus, intra-cisterna magna delivery of GDNF to aged rats improved β-adrenergic receptor function and reduced stress related signaling of bcl-2 in the aged F344 rats to a level similar to that observed in young rats.

    Original languageEnglish (US)
    Pages (from-to)309-316
    Number of pages8
    JournalMicroscopy Research and Technique
    Volume54
    Issue number5
    DOIs
    StatePublished - Sep 1 2001

    Keywords

    • Aging
    • Bcl-2
    • Cerebellum
    • GDNF
    • Norepinephrine

    ASJC Scopus subject areas

    • Anatomy
    • Histology
    • Instrumentation
    • Medical Laboratory Technology

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