Biochemical Studies on Degenerative Neurological Disorders: 1. Acute Experimental Encephalitis

Abstract

—Weanling mice were either injected with viruses or fed cuprizone. Changes in total activity of two cathepsins and two β‐glycosidases were characteristic of each of the five acute encephalopathies studied. Comparisons made between morphological change and hydrolase activity shows that β‐galactosidase and cathepsin A may be useful indices of neuronal degeneration and cellular infiltration into white matter, respectively. β‐Glucuronidase appears to be a particularly sensitive index of cellular reactions to injury. Cathepsin D activity does not appear to reflect any one type of neural cell. Although the morphological changes included neuronal degeneration, perivascular cuffing with mononuclear cells, astrocytic hypertrophy and microgliosis none of the experimental conditions mimicked biochemical changes in multiple sclerosis or senile dementia. The measurement of lysosomal enzymes appears to be a more sensitive indication of acute neurological disorder than the screening of brain proteins by polyacrylamide gel clectrophoresisor the measurement of enzymes (acetylcholinesterase, DOPA decarboxylase and carbonic anhydrase) characteristic of neural cells.

Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease.

“…These results extend earlier studies (7,8,23,24). We also observed striking differences in the distribution of lysosomal hydrolases between neurons and glia, confirming conclusions from earlier biochemical analyses that lysosomes of different neural cell types are heterogeneous in enzyme composition (25,26). CB and HEX were particularly enriched in neurons compared with glial cells.…”

Subcellular Pathology of Human Neurodegenerative Disorders: Alzheimer‐Type Dementia and Huntington's Disease

“…These increases in enzyme activities are unlikely to be due to tissue shrinkage, as activities of other lysosomal enzymes were unchanged. Studies in experimental animals have shown that brain lysosomal glycoside hydrolase activities increase after infection with some conventional viruses (Bowen et al, 1974;Suckling et al, 1976) and also after the slow virus diseases scrapie (Millson and Bountiff, 1973) and Creutzfeldt-Jakob disease (Annunziata and Federico, 1981). The pattern of changes was not found to be specific to the disease studied and also occurs in the reactive gliosis induced in rodents by the toxin cuprizone (Kimberlin et al, 1976).…”

A biochemical method for assessing the neurotoxic effects of misonidazole in the rat

“…There is also evidence that 3-galactosidase can be regarded as a neuronal marker in the CNS (Sinha & Rose, 1972) and that neuronal damage or loss is accompanied by a reduction in the activity of this enzyme, e.g. in the encephalopathy produced by Semliki Forest virus (Bowen et al, 1974). On the basis of this evidence the results shown in Tables IV and V suggest that MISO can induce degenerative changes in the rat cerebellum.…”

“…This is particularly true of degeneration in which cellular proliferation is a feature, e.g. the encephalopathy produced by the copper-chelating agent cuprizone (Bowen et al, 1974). There is also evidence that 3-galactosidase can be regarded as a neuronal marker in the CNS (Sinha & Rose, 1972) and that neuronal damage or loss is accompanied by a reduction in the activity of this enzyme, e.g.…”