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| Craig D. Hardman |
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Prince of Wales Medical Research Institute, Barker Street, Randwick NSW 2031, Australia
e-mail: craig.hardman@unsw.edu.au |
Poster Presentation: |
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| Quantitative comparison of the basal ganglia across diseases and mammalian species. |
| Craig D. Hardman, George Paxinos and Glenda M. Halliday | |
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Prince of Wales Medical Research Institute, Barker Street, Randwick NSW 2031, Australia |
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| Comparison of the pattern and extent of neurodegeneration within the basal ganglia may provide insights into the role extrapyramidal circuits play in disorders of movement. Further, comparison of the basal ganglia across species aids in our endeavours to model and subsequently interpret disorders of the extrapyramidal system in laboratory animals. The volumes, total numbers of neurones and numbers of neurones containing detectable levels of the calcium binding protein parvalbumin were estimated for the subthalamic nucleus, external and internal globus pallidus and the substantia nigra pars reticulata and compacta of 5 human controls, 6 Parkinson’s disease (PD) cases, 6 progressive supranuclear palsy (PSP) cases, 4 baboons, 4 macaques, 4 marmosets and 4 rats. The boundaries of each nucleus were defined in each subject by immunohistochemistry for striatal afferents. Total numbers of Nissl-stained and parvalbumin immunoreactive neurones were calculated using the fractionator technique. Comparisons between species were related to brain mass. All PD and PSP cases had gross rigidity and akinesia at death and there was substantial loss of substantia nigra pars compacta neurones (76±9% loss in PD, 70±3% loss in PSP). Only in PSP were other basal ganglia structures reduced (61±16% loss of subthalamic, 31±23% loss of external globus pallidus, 50±24% loss of internal globus pallidus and 61±25% loss of substantia nigra pars reticulata neurones). Across species, the external globus pallidus had consistently more neurones relative to the internal globus pallidus, subthalamic nucleus and the substantia nigra pars compacta which had similar neuronal numbers within each species. The substantia nigra pars reticulata had proportionally more neurones in rats than in primates (especially humans). The distribution of substantia nigra pars compacta neurones varied substantially between rats and primates (very few ventrally located neurones in rats) with humans containing fewer substantia nigra pars compacta neurones than other primates. The reduction in substantia nigra pars compacta neurones in humans suggests less dopaminergic regulation of the basal ganglia system compared with other species. The consistency in the number of internal globus pallidus neurones across all species, combined with the reduction in substantia nigra pars reticulata neurones in humans, suggests a greater emphasis on output pathways through the internal globus pallidus and that there are proportionally more subthalamic and external globus pallidus neurones in humans. All of these findings will be discussed in relation to the current theories regarding the pathophysiology of extrapyramidal disorders. |
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