title: Assessing nigrostriatal dysfunctions by pharmacological MRI in parkinsonian rhesus macaques.
abstract: New imaging techniques are needed to longitudinally monitor the development, progression and treatment of Parkinson's disease. The present study was designed to test whether the blood oxygenation level-dependent (BOLD) response to dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated to specific histological and behavioral features of the parkinsonian state. Nine adult rhesus monkeys were rendered hemiparkinsonian by intracarotid administration of MPTP. Three months after MPTP treatment, the trained, MRI-adapted awake animals were scanned with a phMRI technique while being administered a presynaptic (D-amphetamine) or postsynaptic (apomorphine) dopamine stimulating agents. The primary findings were (1) the putamen and substantia nigra (SN) but not the caudate nucleus displayed significant BOLD responses to these dopaminergic drugs; (2) a significant relationship was found between amphetamine-evoked activation and the number of surviving dopamine neurons in the SN, which was also correlated with bradykinesia; and (3) inverse relationships were seen in response to apomorphine and amphetamine stimulation between the MPTP-lesioned and unlesioned putamen and SN. The results suggest that phMRI may prove useful for longitudinally monitoring the progression and treatment of PD.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA. zzhan01@pop.uky.edu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Anders H
authors.initials: AH
authors.lastname: Andersen
authors.forename: Yi
authors.initials: Y
authors.lastname: Ai
authors.forename: Aaron
authors.initials: A
authors.lastname: Loveland
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hardy
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: Don M
authors.initials: DM
authors.lastname: Gash
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D002421:Caudate Nucleus / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000494:pharmacology; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D011699:Putamen / Q000187:drug effects / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D007980:Levodopa; D004298:Dopamine