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. Microsc. Res. Tech. 54:309–316, 2001. © 2001 Wiley‐Liss, Inc.