Dopaminergic imaging of nonmotor manifestations in a rat model of Parkinson's disease by fMRI

Nonmotor manifestations determine the life quality of patients with Parkinson's disease (PD). Identification of the nonmotor symptoms in PD as definite changes will represent a milestone in its diagnosis. Outcome measures that characterize nonmotor manifestations with specificity for dopaminerg...

Full description

Bibliographic Details
Main Authors: Chiao-Chi V. Chen, Yen-Yu I. Shih, Chen Chang
Format: Article
Language:English
Published: Elsevier 2013-01-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996112002689
Description
Summary:Nonmotor manifestations determine the life quality of patients with Parkinson's disease (PD). Identification of the nonmotor symptoms in PD as definite changes will represent a milestone in its diagnosis. Outcome measures that characterize nonmotor manifestations with specificity for dopaminergic deficiency are essential to that goal. Pain is a prevalent sensory disturbance in PD patients. The prevalence was reported to be up to 83%. Nociceptive stimuli under normal conditions elicit decreases in cerebral blood volume (CBV) in the striatum via dopaminergic neurotransmission. This nociception-induced CBV response is potentially to be defined as a characteristic of the pain symptom of PD. To validate this concept, steady-state CBV-weighted functional magnetic resonance imaging with iron oxide nanoparticles was employed to measure CBV changes in parkinsonian rats. Tyrosine hydroxylase immunohistology was used to identify the dopaminergic integrity to corroborate the imaging findings. Additional experiments that tested pain responses in parkinsonism were also carried out. The results revealed that the lesioned striatum exhibited a weakened CBV decrease in response to the nociceptive stimulus. This weakened CBV response occurred mainly in areas with dopaminergic denervation. A strong correspondence was observed between the distributions of the nociception-induced CBV responses and dopaminergic innervation. The persisting CBV signals in the striatum were abolished by the D2/D3 antagonist eticlopride. The findings of these behavioral, neuroimaging, immunohistological, and pharmacological experiments demonstrate that pain in a rat model of PD can be characterized by nociception induced striatal CBV signal changes with specificity for dopaminergic dysfunction.
ISSN:1095-953X