Monoaminergic and metabolic Positron Emission Tomography of unilateral and bilateral 6-OHDA rat models of Parkinson's disease: a longitudinal in-vivo study. | 15º Congreso Nacional de la Sociedad Española de NeuroCiencia (25-27 de Septiembre de 2013. Oviedo, Spain)

Abstract

Parkinson´s disease (PD) is characterized by nigro-striatal loss and dopaminergic striatal depletion. The aim of this work is to characterize in-vivo a time-course pattern of functional changes associated with dopaminergic striatal reduction in rat models of PD using Positron Emission Tomography (PET).

Forty-four male Sprague-Dawley rats (300-350gr) were used. PET imaging with monoaminergic (11C-(+)-α-dihydrotetrabenazine; 11C-DTBZ) and metabolic (18F-fluorodeoxyglucose; 18F-FDG) radiotracers were performed in a longitudinal study during 6 weeks of the following groups: a) unilaterally lesioned rats by injection of 4µg/4µl (low dose) and 8µg/4µl (high dose) of 6-hydroxydopamine (6-OHDA) in the left median forebrain bundle; and b) bilateral lesion model, in rats receiving intraventricular injection of 100µg/4µl/day of 6-OHDA during 7 days. At the 8th week, the glucose metabolism was also evaluated ex vivo by 18F-FDG autoradiography. Bilaterally lesioned animals were not assessed with metabolic analyses.

11C-DTBZ PET images showed a significant decrease of Striatal Binding (SB) values one week after the lesion (35% SB in the low and 20% SB in the high dose group of unilateral model, and 50% SB in the bilateral model). In the 6th week, no significant differences in these values were found in the unilaterally lesion rats, whereas animals with bilateral lesion showed a higher binding value (65% SB). Remarkably, the metabolic PET study in the unilateral model revealed hypometabolism in ipsilateral somatosensory cortex and hypermetabolism in contralateral entorhinal cortex since the 2nd week onwards. Additionally, the autoradiography analysis showed hypometabolism in bilateral somatosensory cortex and ipsilateral caudate-putamen, motor cortex and thalamus, and also hypermetabolism in the contralateral entorhinal cortex.

11C-DTBZ PET is a sensitive method to ascertain dopaminergic depletion in both the bilateral and, unilateral 6-OHDA rat models. 18F-FDG studies showed a dynamic metabolic pattern that can provide useful in vivo information to monitor brain changes.