Abstract
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Objectives Dopamine transporter (DAT) imaging in animal models of Parkinson’s disease (PD) is an important tool for studying pathogenic mechanisms and therapeutic strategies in human PD. Thus, it is important to understand the time course of the loss in DATs in animal models of PD. In the present study, we investigated the time course of striatal DAT loss in striatal 6-hydroxydopamine (6-OHDA) rat model of PD using [123I]beta-CIT and small animal SPECT.
Methods Following baseline DAT imaging, the neurotoxic lesions of the left striatum were performed by injecting 20 μg 6-OHDA in male Sprague-Dawley rats. Serial DAT images were acquired up to 16 weeks after the lesioning using [123I]beta-CIT and small animal SPECT. Striatal binding potential (BP) was calculated as striatal-to-cerebellar uptake ratio - 1 at 2 h after [123I]beta-CIT injection. Tyrosine hydroxylase staining was performed to confirm the success of the striatal lesion and to compare with DAT imaging data.
Results During the initial four weeks after lesion, BP in the lesioned striatum was decreased by 40.2 ± 7.8% (P < 0.0001), compared with the baseline level, in a curvilinear manner, with the decline rate of 22.3 ± 8.0%/week during the first two weeks postlesion. During 6-16 weeks after lesion, the BP was restored gradually, reaching 85.5 ± 4.8% of the baseline level at 16 week postlesion. The BP values were correlated well with the tyrosine hydroxylase staining results.
Conclusions These results indicate a slow partial loss of striatal DATs in the striatal 6-OHDA rat model of PD, mimicking the slow progression of PD. However, they also demonstrate that this PD model allows a progressive recovery of DATs commencing 4-6 week postlesion. These data may have important implications for designing and interpreting DAT imaging studies in the striatal 6-OHDA rat model of PD