Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington’s disease

Abstract

The centromedian-parafascicular complex represents a nodal point in the neuronal loop comprising striatum--globulus pallidus--thalamus--striatum. Striatal neurone degeneration is a hallmark in Huntington's disease and we were interested in estimating total neurone and glial number in this thalamic nuclear complex. Serial 500-microns-thick gallocyanin-stained frontal sections of the left hemisphere from six cases of Huntington's disease patients (three females, three males) and six age- and sex-matched controls were investigated applying Cavalieri's principle and the optical disector. Mean neurone number in the controls was 646,952 +/- 129,668 cells versus 291,763 +/- 60,122 in Huntington's disease patients (Mann-Whitney U-test, P < 0.001). Total glial cell number (astrocytes, oligodendrocytes, microglia, and unclassifiable glial profiles) was higher in controls with 9,544,191 +/- 3,028,944 versus 6,961,989 +/- 2,241,543 in Huntington's disease patients (Mann-Whitney U-test, P < 0.021). Considerable increase of fibrous astroglia within the centromedian-parafascicular complex could be observed after Gallyas' impregnation. Most probably this cell type enhanced the numerical ratio between glial number and neurone number (glial index: Huntington's disease patients = 24.4 +/- 8.1; controls = 15.0 +/- 5.2; Mann-Whitney U-test, P < 0.013). The neurone number in the centromedian-parafascicular complex correlated negatively, although statistically not significantly, with the striatal neurone number. This lack of correlation between an 80% neuronal loss in the striatum and a 55% neurone loss in the centromedian-parafascicular complex points to viable neuronal circuits connecting the centromedian-parafascicular complex with cortical and subcortical regions that are less affected in Huntington's disease.

Increased brain tissue sodium concentration in Huntington's Disease — A sodium imaging study at 4T

“…Although huntingtin is ubiquitously expressed, the expression of huntingtin with a polyglutamin repeat expansion leads to selective neuronal cell death in the striatum and cortex. Neuropathological changes have been found to be most pronounced in the striatum (Reiner et al, 1988;Vonsattel and DiFiglia, 1998) but there are also clear effects in the cerebral cortex, globus pallidus, thalamus, subthalamic nucleus, substantia nigra, hypothalamus, and cerebellum in later stages of the disease (Gabery et al, 2010;Heinsen et al, 1996;Petersen and Bjorkqvist, 2006;Thu et al, 2010;Vonsattel and DiFiglia, 1998). Overall, striatal atrophy correlates with that of other brain regions (Vonsattel, 2008) and the brunt of the degenerative process involves the striatum, a key component of the basal ganglia, an interconnected set of subcortical nuclei involved in the regulation of action (Balleine et al, 2009).…”

The Neuropathology of Huntington’s Disease

“…A recent MRI analysis (Kassubek et al 2005) shows that there is variability in thalamic degeneration which agrees with neuropathological studies in the postmortem brain. The main regions of atrophy described in the thalamus so far are that of the dorsomedial nucleus (DM) (Heinsen et al 1999), the centromedial/ventrolateral nucleus (CM/VLa) nuclear group, and the centromedial/parafascicular nucleus (Heinsen et al 1996). The parafascicular nucleus is part of the thalamic intralaminar nuclear group which projects to the striatum and its terminals are thought to label specifically for VGlut2 based on animal studies (Doig et al 2010;Deng et al 2013).…”

The Ventral Striatopallidum and Extended Amygdala in Huntington Disease

“…The striatal atrophy is due to the progressive loss of medium-sized GABAergic striatal neurons (Heinsen et al, 1994), which comprise approximately 90% of all neurons in the striatum. Cortical, subcortical and brainstem areas with grey and white matter changes are also affected (de la Monte et al, 1988;Dumas et al, 2012;Heinsen et al, 1996;Heinsen et al, 1999;Rosas et al, 2003;Rüb et al, 2009;Schmitz et al 1999;Tabrizi et al, 2011). Up to now, there is no cure for HD.…”