Positron emission tomography neuroimaging of [F]fluorodeoxyglucose uptake and related behavior in the -/- rat model of Parkinson disease.

INTRODUCTION

Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior.

METHODS

(n = 12) and WT (n = 14) rats were imaged by [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam.

RESULTS

Relative glucose metabolism was significantly different in rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, -/- rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra.

CONCLUSION

FDG PET reveals abnormalities in relative regional brain glucose metabolism in rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the PD model.