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Abstract
The 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease (PD) has been used to evaluate the nigrostriatal pathway. The aim of this work was to explore the relationship between the degree of 6-OHDA-induced dopaminergic degeneration and [(123)I]FP-CIT binding using single photon emission computed tomography (SPECT). Fourteen rats received a 6-OHDA injection (4 or 8 µg) into the left medial forebrain bundle. After 3 weeks, magnetic resonance imaging and scans with a small-animal SPECT system were performed. Finally, the nigrostriatal lesion was assessed by immunohistochemical analysis. Immunohistochemical analysis confirmed two levels of dopaminergic degeneration. Lesions induced by 6-OHDA diminished the ipsilateral [(123)I]FP-CIT binding by 61 and 76%, respectively. The decrease in tracer uptake between control and lesioned animals was statistically significant, as was the difference between the two 6-OHDA lesioned groups. Results concluded that [(123)I]FP-CIT SPECT is a useful technique to discriminate the degree of dopaminergic degeneration in a rat model of PD.
Highlights
Single photon emission computed tomography (SPECT) has become a useful neuroimaging technique for in vivo evaluation of neurotransmission systems in both clinical diagnosis [1] and basic research [2]
In parallel to this study, we have evaluated a 6-OHDA rat model using immunohistochemistry, magnetic resonance imaging (MRI) and [123I]FP-CIT single photon emission computed tomography (SPECT)
The aim of this work was to confirm the relationship between the degree of dopaminergic degeneration and neuroimaging [123I]FP-CIT SPECT on an experimental rat model of Parkinson’s disease (PD)
Summary
Single photon emission computed tomography (SPECT) has become a useful neuroimaging technique for in vivo evaluation of neurotransmission systems in both clinical diagnosis [1] and basic research [2]. SPECT allows the evaluation of presynaptic dopaminergic terminals of the nigrostriatal neurotransmission system. Presynaptic dopamine function is associated with the dopamine transporter (DAT). The DAT is responsible for reuptake of dopamine from the synaptic cleft and has proved to be a sensitive indicator of the nigrostriatal dopaminergic function. Parkinson’s Disease (PD) is related to a degeneration of the nigrostriatal dopaminergic system and SPECT with [123I]-N-omega-fluoropropyl-2βcarbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT, DaTSCAN; GE Healthcare), a radiotracer that binds DAT, has been shown to be useful for PD diagnosis [1,3]. By studying models of PD using [123I]FP-CIT SPECT, an increasing number of compounds with neuroprotective properties [4] could be examined along with other therapeutic approaches [5] in PD treatment
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