Objective: To evaluate the locus coeruleus (LC) activity in subjects with Parkinson’s disease (PD) at an early stage. Background: The LC is the major site of noradrenaline neurons in the central nervous system. The LC plays an important role in the pathophysiology of PD (i) as a site of neuronal degeneration; (ii) as the anatomical origin of projections modulating dopaminergic action of the substantia nigra; (iii) as a structure under dopaminergic inhibitory control from the ventral tegmental area. Methods: We retrospectively reviewed clinical and imaging data of 94 subjects with PD at an early clinical stage (Hoehn and Yahr stage 1-2) who underwent single photon computed tomography imaging with FP-CIT ([123I] N-x-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane). While FP-CIT is commonly used as an in vivo marker of dopamine uptake transporters, it has documented sensitivity also to noradrenaline transporters, allowing noradrenergic LC activity to be studied simultaneously. Binding values were compared with 15 healthy subjects. Two different image analyses were performed: a voxel-based whole brain analysis and a volume of interest analysis of a priori defined brain regions. Results: Average FP-CIT uptake in the putamen and caudate nucleus was significantly reduced in PD subjects (43% and 57% on average, respectively; p<0.001). In contrast, subjects with PD showed an increased uptake in the LC area (166% on average; p<0.001) in both analyses. LCuptake correlated negatively with striatal FP-CIT binding values (caudate: contralateral, q5-0.35, p<0.01 and ipsilateral q5-0.3, p<0.01; putamen: contralateral, q5-0.3, p<0.01 and ipsilateral q5-0.3, p<0.01). Conclusions: These findings are consistent with an up-regulation of noradrenaline reuptake in the LC area of patients with PD at an early stage, which is well compatible with enhanced noradrenaline release, and a compensating activity for degeneration of dopaminergic nigrostriatal projections. Potential functions of LC in PD can be ascribed (i) to an interplay of catecholamine systems with one amine cross-talking with receptors belonging to the other system and (ii) to a neuro-modulatory, metabotroic and trophic extra-synaptic activity of noradrenaline affecting local metabolism of areas of projection.
|Titolo:||Enhanced catecholamine transporter binding in the locus coeruleus of patients with early Parkinson's disease|
ISAIAS, IOANNIS UGO (Primo)
CRENNA, PAOLO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||2011|
|Appare nelle tipologie:||01 - Articolo su periodico|