Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy — an immunocytochemical and Gallyas silver impregnation study

Abstract

A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.

Distribution and dynamic process of neuronal cytoplasmic inclusion (NCI) in MSA: Correlation of the density of NCI and the degree of involvement of the pontine nuclei

“…The inclusion was sharply demarcated and appeared pale. In recent studies NCI have been reported mainly in the pons, but few NCI have been reported in the hipocampus, caudate, putamen, amygdala, periaqueductal gray matter, red nucleus, substantia nigra, pontine nucleus, nucleus ambiguus, inferior olivary nucleus 17–19,26,28 . In the present study the inclusions were observed only in the pontine nucleus (19 cases) and hippocampus (one case).…”

“…All cases of MSA have GCI, but not all brains containing GCI necessarily have MSA 4,5 . Recent studies reported that GCI in MSA were closely associated with tau, tubulins and microtubule‐associated protein (MAP) 5, and not with paired helical filaments, MAP 1, MAP 2, neurofilament protein, GFAP, or synaptophysin 15–22 . Corresponding to previous studies, many GCI stained positive with antibodies to ubiquitin and α‐synuclein in all the MSA cases examined 10–14 .…”

Involvement of precerebellar nuclei in multiple system atrophy

“…These Gallyas‐type silver techniques utilize the physical development of nucleation sites and thereby permit tight control of the entire staining procedure [35,36]. Originally, the Gallyas silver‐iodide technique was intended for use in identifying intraneuronal neurofibrillary changes of the Alzheimer type [35], but it has also been widely employed to visualize GCIs [48,51,61].…”

Decrease in neuronal density in the cerebral cortex in multiple system atrophy

“…The specificity of GCIs and their value in the histological diagnosis of MSA have been confirmed in a number of laboratories (Nakazato el al., 1990;Horoupian and Dickson, 199 1 ;Kato ef al., 199 1 ;Abe et al, 1992;Arai et al, 1992;Costa ef al., 1992;Daniel and tlawkes, 1992;Kobayashi et al, 1992;Mochizuki et ul., 1992;Murayama et al, 1992;Wenning el al., 1995). The intracellular accumulation of the tubular structures, identified as forming inclusions, in oligodendroglia and neurons has been demonstrated as the basic neuropathological alteration in MSA (Papp and Lantos.…”

“…Whilst the earlier study (Papp el al., 1989) showed a high density of GCls extensively in the brain, including regions not previously thought to be affected in MSA, significant numbers of neuronal cytoplasmic and nuclear inclusions were only present in a small proportion of some neuronal populations (Papp and Lantos, 1992). More recently a sensitive silver impregnation technique (Gallyas and Wolff, 1986), has been employed to carry out semiquantitative mapping of GCls in MSA and to compare the severity of oligodendroglial degeneration with that of the neuronal changes (Papp and Lantos, 1994).…”