Morphometric analysis of the prefrontal cortex in Huntington's disease

Sotrel, Ana; Paskevich, Peter A.; Kiely, Dan K.; Bird, E. D.; Williams, Roger; Myers, Richard H.

doi:10.1212/wnl.41.7.1117

Cited by 185 publications

(143 citation statements)

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“…However, this cortical area has been demonstrated to exhibit hypometabolism in patients with HD, studied by a variety of noninvasive functional imaging methods (31). Similarly, neuropathological studies have highlighted this area as one exhibiting prominent neurite pathology in this disease (32,33). Our studies, confirmed by results of the studies of postmortem material from HD patients, suggests that further investigation of the anterior cingulate cortex in HD is clearly warranted.…”

Section: Discussionsupporting

confidence: 61%

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Turmaine

Raza²,

Mahal³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

398

266

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Huntington's disease (HD) is a fatal inherited neurodegenerative disorder characterized by personality changes, motor impairment, and subcortical dementia. HD is one of a number of diseases caused by expression of an expanded polyglutamine repeat. We have developed several lines of mice that are transgenic for exon 1 of the HD gene containing an expanded CAG sequence. These mice exhibit a defined neurological phenotype along with neuronal changes that are pathognomonic for the disease. We have previously observed the appearance of neuronal intranuclear inclusions, but did not find evidence for neurodegeneration. In this study, we report that all lines of these mice develop a late onset neurodegeneration within the anterior cingulate cortex, dorsal striatum, and of the Purkinje neurons of the cerebellum. Dying neurons characteristically exhibit neuronal intranuclear inclusions, condensation of both the cytoplasm and nucleus, and ruffling of the plasma membrane while maintaining ultrastructural preservation of cellular organelles. These cells do not develop blebbing of the nucleus or cytoplasm, apoptotic bodies, or fragmentation of DNA. Neuronal death occurs over a period of weeks not hours. We also find degenerating cells of similar appearance within these same regions in brains of patients who had died with HD. We therefore suggest that the mechanism of neuronal cell death in both HD and a transgenic mouse model of HD is neither by apoptosis nor by necrosis.

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Section: Discussionsupporting

confidence: 61%

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Turmaine

Raza²,

Mahal³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

398

266

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“…Our quantitative results of reduced cortical nerve cell number in Huntington's disease patients substantiate qualitative observations [5,19,20,40,46,80,83,99,116] and extend previous quantitative investigations on cortical atrophy [28,74,75,79] and reduced nerve cell density [25,53,108,110].…”

Section: Methodological Considerationssupporting

confidence: 90%

“…We think this phenomenon is due to the degeneration of layer Va pyramidal cells and a subsequent closer spacing of layer IV granule cells. A recent quantitative investigation failed 329 to demonstrate conspicuous astroglial proliferation in the prefrontal cortex of Huntington's disease patients [108]. Our results are in agreement with the neurochemical investigations of Ellison et al [35], who found reduced glutamate but unchanged GABA concentrations in the frontal, parietal, and occipital lobes.…”

Section: Laminar and Areal Versus Diffuse Nerve Cell Losssupporting

confidence: 93%

“…Neuronal loss in prefrontal and premotor fields appeared intermediate between primary sensory and parietal as well as temporal fields. Thus, our results are congruent with reports of an overall reduced nerve cell density [108], selective loss of pyramidal neurones containing a nonphosphorylated neurofilament reactive to a monoclonal (SMI-32) antibody [25], reduced nerve cell density in layers V and VI [108,109], and probable hypertrophy of a subset of pyramidal neurones [109]. One conspicuous feature in low-power microscopic inspection of serial frontal sections was a clearly demarcated layer IV in isocortical fields.…”

Section: Laminar and Areal Versus Diffuse Nerve Cell Losssupporting

confidence: 92%

“…It is argued that atrophy in the striate body disrupts the neuronal loop between prefrontal cortical regions and thalamic feedback [3,4,71,85,98,115]. Other investigators explain cognitive deficits by global cortical, subcortical, and white matter atrophy [28,79], selective laminar loss of a nonphosphorylated neurofilament (SMI-32 ir) bearing pyramidal cells [25], and reduced nerve cell density in layers V and VI of the prefrontal cortex [108,109]. In these investigations, nerve cell density estimations were thought to reflect total neuronal loss.…”

Section: Introductionmentioning

confidence: 99%

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Cortical and striatal neurone number in Huntington's disease

Heinsen¹,

Strik²,

Bauer³

et al. 1994

Acta Neuropathol

151

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The total cortical and striatal neurone and glial numbers were estimated in five cases of Huntington's disease (three males, two females) and five ageand sex-matched control cases. Serial 500-l-lm-thick gallocyanin-stained frontal sections through the left hemisphere were analysed using Cavalieri's principle for volume and the optical disector for cell density estimations. The average cortical neurone number of five controls (mean age 53±13 years, range 36-72 years) was 5.97x 10 9 ±320x 10 6 , the average number of small striatal neurones was 82 X 10 6 ± 15.8 X 10 6 • The left striatum (caudatum, putamen, and accumbens) contained a mean of 273 X 10 6 ±53 X 10 6 glial cells (oligodendrocytes, astrocytes and unc1assifiable glial profiles). The mean cortical neurone number in Huntington's disease patients (mean age 49±14 years, range 36-75 years) was diminished by about 33 % to 3.99x10 9 ±218x10 6 nerve cells (P : : ; : : : : 0.012, MannWhitney V-test). The mean number of small striatal neurones decreased tremendously to 9.72 X 10 6 ±

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Neuronal and Glial Somal Size in the Prefrontal Cortex

Rajkowska¹,

Selemon²,

Goldman‐Rakic³

1998

Arch Gen Psychiatry

484

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Distinct cytometric abnormalities support the hypothesis that neuronal degeneration in the prefrontal cortex is not a prominent feature of the neuropathological changes in schizophrenia, although an ongoing process in Huntington disease. Rather, schizophrenia appears to involve more subtle abnormalities, with the largest corticocortical projection neurons of layer IIIc expressing the greatest somal reduction.

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Morphometric analysis of the prefrontal cortex in Huntington's disease

Cited by 185 publications

References 0 publications

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Cortical and striatal neurone number in Huntington's disease

Neuronal and Glial Somal Size in the Prefrontal Cortex

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