title: Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.
abstract: The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain.
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Andersen
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hardy
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Forman
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Don M
authors.initials: DM
authors.lastname: Gash
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Grondin
authors.affiliation: Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA. Electronic address: Zzhan01@uky.edu.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000375:Aging / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D001552:Benzazepines / Q000494:pharmacology; D003937:Diagnosis, Differential; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009043:Motor Activity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D020891:Raclopride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; C534628:SCH 23390; D020891:Raclopride; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine
keywords: Aging; Apomorphine; MPTP; Parkinsonism; Pharmacologic MRI; Raclopride; SCH23390