Dopamine‐transporter levels drive striatal responses to apomorphine in Parkinson's disease

Brain and Behavior

Luca Passamonti²  Maria Salsone²  Nicola Toschi³  Antonio Cerasa⁵  Marco Giannelli¹  Carmelina Chiriaco⁵  Giuseppe Lucio Cascini⁴  Francesco Fera² 

[1] Unità operativa di Fisica Medica, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italia;Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi “Magna Graecia”, Catanzaro, Italia;Dipartimento di Biopatologia e Diagnostica per Immagini, Università degli Studi di Roma “Tor Vergata”, Roma, Italia;Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi “Magna Graecia”, Catanzaro, Italia;Istituto di Scienze Neurologiche (ISN), Consiglio Nazionale delle Ricerche, Catanzaro, Italia

关键词: Cognition;    DAT;    dopamine‐agonist;    fMRI;    Parkinson's disease;    working memory;   

DOI  :  10.1002/brb3.115

来源: Wiley

【 摘 要 】

Abstract

Dopaminergic therapy in Parkinson's disease (PD) can improve some cognitive functions while worsening others. These opposite effects might reflect different levels of residual dopamine in distinct parts of the striatum, although the underlying mechanisms remain poorly understood. We used functional magnetic resonance imaging (fMRI) to address how apomorphine, a potent dopamine agonist, influences brain activity associated with working memory in PD patients with variable levels of nigrostriatal degeneration, as assessed via dopamine-transporter (DAT) scan. Twelve PD patients underwent two fMRI sessions (Off-, On-apomorphine) and one DAT-scan session. Twelve sex-, age-, and education-matched healthy controls underwent one fMRI session. The core fMRI analyses explored: (1) the main effect of group; (2) the main effect of treatment; and (3) linear and nonlinear interactions between treatment and DAT levels. Relative to controls, PD-Off patients showed greater activations within posterior attentional regions (e.g., precuneus). PD-On versus PD-Off patients displayed reduced left superior frontal gyrus activation and enhanced striatal activation during working-memory task. The relation between DAT levels and striatal responses to apomorphine followed an inverted-U-shaped model (i.e., the apomorphine effect on striatal activity in PD patients with intermediate DAT levels was opposite to that observed in PD patients with higher and lower DAT levels). Previous research in PD demonstrated that the nigrostriatal degeneration (tracked via DAT scan) is associated with inverted-U-shaped rearrangements of postsynaptic D2-receptors sensitivity. Hence, it can be hypothesized that individual differences in DAT levels drove striatal responses to apomorphine via D2-receptor-mediated mechanisms.

【 授权许可】

CC BY   
© 2013 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

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