Abstract:
Human globus pallidus volume reduction in HD with differential cell loss between external and internal segments M.K. SINGH-BAINS1,2, H.J. WALDVOGEL1,2, R.L.M. FAULL1,2 1Centre for Brain Research, 2Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand. In Huntington’s disease (HD), there are major pathological changes in the basal ganglia, with major loss of striatal neurons. However, there have been no studies using design-based stereology to assess cell and volume changes in the globus pallidus (GP), the target of striatal output. In our study, 8 HD and 8 normal cases were analysed in detail using unbiased stereological counting methods and 3D volume analysis, to quantify pallidal neurons and investigate volume changes in all segments of the GP. Pallidal neurons were morphologically identified on Nissl-stained 70 µm serial sections, with external (GPe) and internal (GPi) segment boundaries identified using enkephalin and substance-P immunoreactivity. The results show a major reduction in total GP volume in HD, with GPe volume loss being greater than GPi. Preliminary findings show a 54% reduction in GPe volume, with greater reduction corresponding with increasing HD grade (grade 1, 45% decrease; grade 3, 56% decrease). In the GPi, there is an overall 38% reduction in volume, with greater reduction with increasing grade (grade 1, 29% decrease; grade 3, 40% decrease). Pallidal neuron quantification (in progress) shows greater cell loss in the HD GPe compared with GPi. GPe quantification shows a 64% loss of pallidal neurons, with greater cell loss corresponding with increasing grade (grade 1, 40% loss; grade 3, 80% loss). GPi quantification shows a 20% decrease in pallidal neurons. These findings show that there is a greater volume and cellular reduction in the GPe compared to GPi in HD, consistent with neurochemical studies showing that enkephalinergic striatal-GPe fibres degenerate in advance of substance-P striatal-GPi fibres. M.K. SINGH-BAINS1,2, H.J. WALDVOGEL1,2, R.L.M. FAULL1,2 1Centre for Brain Research, 2Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand. In Huntington’s disease (HD), there are major pathological changes in the basal ganglia, with major loss of striatal neurons. However, there have been no studies using design-based stereology to assess cell and volume changes in the globus pallidus (GP), the target of striatal output. In our study, 8 HD and 8 normal cases were analysed in detail using unbiased stereological counting methods and 3D volume analysis, to quantify pallidal neurons and investigate volume changes in all segments of the GP. Pallidal neurons were morphologically identified on Nissl-stained 70 µm serial sections, with external (GPe) and internal (GPi) segment boundaries identified using enkephalin and substance-P immunoreactivity. The results show a major reduction in total GP volume in HD, with GPe volume loss being greater than GPi. Preliminary findings show a 54% reduction in GPe volume, with greater reduction corresponding with increasing HD grade (grade 1, 45% decrease; grade 3, 56% decrease). In the GPi, there is an overall 38% reduction in volume, with greater reduction with increasing grade (grade 1, 29% decrease; grade 3, 40% decrease). Pallidal neuron quantification (in progress) shows greater cell loss in the HD GPe compared with GPi. GPe quantification shows a 64% loss of pallidal neurons, with greater cell loss corresponding with increasing grade (grade 1, 40% loss; grade 3, 80% loss). GPi quantification shows a 20% decrease in pallidal neurons. These findings show that there is a greater volume and cellular reduction in the GPe compared to GPi in HD, consistent with neurochemical studies showing that enkephalinergic striatal-GPe fibres degenerate in advance of substance-P striatal-GPi fibres.