Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration最新文献

Clusterin has been implicated in cell death both in peripheral tissues and in the central nervous system. In the present study, expression of clusterin in the cerebellar cortex was examined in two cases with hypoxic brain damage and in one case with cerebellar infarction. Intense staining of Purkinje cells was observed in each case, and these cells showed the shrunken and pyknotic appearance characteristic of irreversible ischaemic damage. In the cerebella of neurologically normal control cases, as well as in those of some other neurodegenerative diseases, no staining or only punctate staining of Purkinje cells was observed. The results provide additional evidence supporting an association of clusterin with dying neurons in human brain.

This study compared a panel of three different prion protein antibodies with conventional plaque staining methods--Congo Red, Periodic acid Schiff and sulphated Alcian blue--to investigate amyloid plaque formation in cases of human spongiform encephalopathy (HSE). Tissue samples were taken from the cerebellum in nine sporadic cases of Creutzfeldt-Jakob Disease, with plaque formation noted on routine histology, and one case of Gerstmann-Straussler Scheinker syndrome. Using image analysis techniques, a semi-automatic system of plaque quantification was devised to measure the relative performance of these different staining methods. A total figure of percentage tissue area stained positively was returned by the system in each case analysed. A significant statistical correlation was observed among all three antibodies (r > 0.9, P < 0.01, in all comparisons) and a significant improvement was observed when the average antibody staining figures were compared to those of the Alcian blue technique (P < 0.05). The distribution of plaques across the cerebellar layers observed here appears to confirm earlier research findings. A strong correlation was found between staining in the two cerebellar hemispheres (r = 0.97, P < 0.01). This novel image analysis system has considerable potential for objective assessment of the pathology of HSE.

The topographic distribution of brain atrophy in nine patients with parkinsonism-dementia complex of Guam (Guam PDC) was evaluated quantitatively, and compared with that in six Japanese patients with Alzheimer's disease or senile dementia of Alzheimer type (AD), five Japanese patients with progressive supranuclear palsy (PSP), and nine Japanese control subjects. Characteristic features of Guam PDC were as follows: (1) severe atrophy of the frontal and temporal cortex with relative preservation of the white matter; (2) atrophy of the tectum, tegmentum and cerebral peduncle of the midbrain, and (3) atrophy of the tegmentum and base of the upper pons. In contrast, sectional areas of the tectum and cerebral peduncle of the midbrain were relatively well preserved in PSP, while in AD there was no significant atrophy in the brain stem.

The present study examined neurochemical, morphological and functional markers of the nigrostriatal dopamine system in young, intermediate-aged and old squirrel monkeys. Striking reductions in motoric activity were observed with advancing age. significant age-related loss of dopamine occurred in the substantia nigra (70%) and the putamen (30%) but not in the caudate. There was a strong correlation between the reductions in motoric activity and the loss of putamen dopamine. However, nigrostriatal dopamine loss did not appear to be the consequence of age-related loss of dopaminergic nigral neurons since the number of tyrosine immunoreactive cells was not significantly different among the three age groups. These results suggest that the aging squirrel monkey demonstrates the age-related loss of nigrostriatal dopamine thought to occur in humans and identify this non-human primate as a useful model to further investigate the underlying mechanism(s) and functional consequences of age-related decline of the nigrostriatal dopamine system. In addition, the selective loss of dopamine in the putamen but not the caudate parallels the regional vulnerability observed in Parkinson's disease, an age-related neurodegenerative disorder, raising the possibility of a relationship between normal aging and the development of this disease. Finally, because the number of tyrosine hydroxylase (TH) positive cells remains constant with age, these results raise the possibility that therapeutic strategies aimed at increasing dopamine concentrations may benefit elderly individuals.

Expression of the nerve cell adhesion molecule, NCAM, was examined in post-mortem brain samples from patients with Alzheimer's disease (AD) and from age-matched controls. Four major isoforms of NCAM were identified by Western blot analysis 195, 185, 145 and 120 kDa with no differences being observed in either the intensity of individual band staining or in the expression of the constituent NCAM isoforms in AD when compared with controls. Immunohistochemical staining revealed star-shaped NCAM-positive structures with numerous radiating 'processes' or a more protoplasmic shape with short and thick 'processes'. These structures were not obviously more abundant in AD and there was no NCAM immunoreactivity in neuritic plaques or neurofibrillary tangles. This evidence suggests there is no change in NCAM expression in AD.