Abstract
896
Objectives: To determine the effects of high-intensity exercise on DA neurotransmission in the MPTP-lesioned mouse model of PD. To quantify through PET striatal D2 receptors with the high-affinity tracer F-18 Fallypride in C57BL/6J mice undergoing high-intensity exercise vs no exercise.
Methods: Groups of mice: saline, saline+exercise, MPTP, and MPTP+exercise. Saline and MPTP mice were subjected to treadmill exercise (1H/D, 5D/W for 6W), starting 5D after lesioning, when cell death is complete. Fallypride (SA>6000Ci/mmole, 280uCi) was used at the end of the exercise period. Dynamic PET scans were performed with a microPET R4 scanner for 90' after iv tracer administration. Images were reconstructed using MAP algorithm with normalization and attenuation correction. Receptor quantification was preformed using the cerebellum as a reference region. The binding potential was derived using the dynamic model as from M. Honer.
Results: Striatal DA D2 receptor level measured as BP is reduced in the MPTP mouse (BP=4) compared to saline treated mouse (BP=10.5). Exercise leads to a normalization (BP=7) in the MPTP mouse. The results are consistent with our molecular analysis showing an increase in the transcript and protein expression for the DA D2 receptors after exercise in the MPTP mouse.
Conclusions: F-18 Fallypride can discriminate changes in the DA D2 receptor densities within the basal ganglia using the microPET R4 scanner. Exercise leads to changes in DA neurotransmission within the injured basal ganglia, as measured through the BPs. Future studies will examine the effects of high-intensity treadmill exercise on DA D2 receptor density in PD individuals using this PET tracer.
- Society of Nuclear Medicine, Inc.