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We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subjected to treatment with a neurotoxin to(More)
Significant differences have been reported in results from three clinical trials evaluating intraputamenal infusion of glial cell line-derived neurotrophic factor (GDNF) for the treatment of Parkinson's disease. To determine if problems in drug bioavailability could have contributed to the discrepancies between studies, we have analyzed the distribution of(More)
Functional imaging of the non-human primate brain in awake animals is now feasible because of recent methodological advances. Here we detail our procedures for conducting functional MRI (fMRI) studies in rhesus monkeys. Our emphasis has been on analyzing drug-evoked responses within and across test groups, meaning that techniques have had to be developed(More)
Changes in the functional dynamics of dopamine release and regulation in the basal ganglia have been posited to contribute to age-related slowing of motor functions. Here, we report the effects of glial cell line-derived neurotrophic factor (GDNF) on the stimulus-evoked release of dopamine and motor speed in aged monkeys (21-27 years of age; n = 10).(More)
Age-dependent metabolic syndrome (MetS) is a well established risk factor for cardiovascular disease, but it also confers major risk for impaired cognition in normal aging or Alzheimer's disease (AD). However, little is known about the specific pathways mediating MetS-brain interactions. Here, we performed the first studies quantitatively linking MetS(More)
PURPOSE To estimate the relationship between R2 = 1/T2 as measured with a double echo spin echo sequence and total iron concentration in gray matter structures in the brains of aging rhesus monkeys. MATERIALS AND METHODS Using a 1.5-T magnetic resonance (MR) imager, we collected double echo spin echo images of the brains of 12 female rhesus monkeys aged(More)
Functional magnetic resonance imaging (fMRI) is increasingly used in non-human primate research. In the present study, we adapt the familiarization-novelty preference (FNP) procedure used in human infant research to examine visual behavior in alert, unanaesthetized rhesus monkeys that were acclimated to the fMRI environment, but did not undergo behavioral(More)
The powerful trophic effects that glial cell line-derived neurotrophic factor (GDNF) exerts on midbrain dopamine neurones suggest its use in treating Parkinson's disease. However, some important questions remain about the possible therapeutic applications of GDNF. Here we demonstrate that the chronic infusion of 5 or 15 micro g/day GDNF into the lateral(More)
Site-specific delivery of trophic factors in the brain may be important for achieving therapeutic efficacy without unwanted side effects. This study evaluated the site-specific infusion of glial cell line-derived neurotrophic factor (GDNF) into the right putamen of aged rhesus monkeys. After 4 weeks of continuous infusion at a rate of 22.5 microg/day, GDNF(More)
For these studies, young (8-9 years), middle-aged (14-17 years) and aged (23-28 years) rhesus monkeys were used as a model of normal aging in humans to investigate changes in dopamine (DA)-containing neurons in senescence. Aged monkeys exhibited significant age-related motoric declines as compared to the young animals. In vivo microdialysis studies showed(More)