Postural changes after lesions of the substantia nigra pars reticulata in hemiparkinsonian monkeys.
Current neurosurgical strategies target overactive brain regions including the subthalamic nucleus, globus pallidus and thalamus to control various symptoms of Parkinson's disease. Subthalamotomy improves akinesia and can induce postural deficits in both parkinsonian humans and animals, pallidotomy improves limb dyskinesia and more variably, distal bradykinesia whilst thalamotomy improves tremor. Because the SNr also becomes overactive in PD and there are few surgical studies in parkinsonian primates, we therefore evaluated the effects of lesioning the SNr in hemiparkinsonian marmosets to establish the effects on symptomatology. Nine monkeys received unilateral 6-hydroxydopamine (6-OHDA) lesions. Seven weeks later, four received kainic acid lesions of the SNr. Behavioural tests were performed prior to 6-OHDA surgery and then fortnightly for 14 weeks. Unilateral 6-OHDA lesions induced ipsilateral postural bias, ipsilateral rotation after amphetamine injection and bradykinesia. Whilst, SNr lesions significantly altered the direction of head position and amphetamine-induced rotation relative to 6-OHDA lesions, there was no improvement in 6-OHDA-induced reaching deficits or sensorimotor neglect. Unbiased quantitation of the nigral lesions showed on average 88% loss of dopaminergic neurons after 6-OHDA lesions and 77% loss of non-dopaminergic neurons after SNr lesions. Our results demonstrate that the SNr is important in body orientation changes in parkinsonism.
Henderson
Jasmine M
JM
Prince of Wales Medical Research Institute, University of New South Wales, Sydney, Australia. jasmine@med.usyd.edu.au
Stanic
Davor
D
Tomas
Doris
D
Patch
Justin
J
Horne
Malcolm K
MK
Bourke
Darren
D
Finkelstein
David I
DI
D018663:Adrenergic Agents / Q000633:toxicity; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002144:Callithrix; D002452:Cell Count; D004195:Disease Models, Animal; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000503:physiopathology*; D011187:Posture / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013378:Substantia Nigra / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D018690:Excitatory Amino Acid Agonists; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D007608:Kainic Acid