Neurodegenerative changes in rat produced by lithium treatment.

Lithium is extensively used in psychiatric practice for the prevention and treatment of manic-depressive disorders. However, neurotoxicity attributed to lithium salts within therapeutic doses was also reported in patients, manifested by transient or persistent neurological deficits. In this study, morphological changes were examined in rats treated acutely and chronically with lithium. Pathological changes were observed in different brain regions including cerebral cortex, cerebellum, medulla oblongata, mesencephalon, thalamus, and pons, using a silver-copper impregnation technique for neurodegeneration. Vacuolization of brain tissue with subsequent formation of spongiosis was the prominent morphological feature following lithium administration. The zones of spongiosis were irregularly distributed throughout the brain. More intensive compact areas with spongiform changes were found in the cerebral cortex and medulla oblongata. Less pronounced vacuolization was noted in the pons and thalamic region. The cerebellum and mesencephalon appeared least affected. Vacuolization in the cerebellar cortex was found at loci with Purkinje cells, but the classical picture of spongiosis was not apparent. Data indicate that both acute and chronic lithium intoxication accelerated neurodegenerative changes normally seen with normal brain aging.

Developmental study of tripeptidyl peptidase I activity in the mouse central nervous system and peripheral organs.

Tripeptidyl peptidase I (TPPI) - a lysosomal serine protease - is encoded by the CLN2 gene, mutations that cause late-infantile neuronal ceroid lipofuscinosis (LINCL) connected with profound neuronal loss, severe clinical symptoms and early death at puberty. Developmental studies of TPPI activity levels and distribution have been done in the human and rat central nervous systems (CNS) and visceral organs. Similar studies have not been performed in mouse. In this paper, we follow up on the developmental changes in the enzyme activity and localization pattern in the CNS and visceral organs of mouse over the main periods of life - embryonic, neonate, suckling, infantile, juvenile, adult and aged - using biochemical assays and enzyme histochemistry. In the studied peripheral organs (liver, kidney, spleen, pancreas and lung) TPPI is present at birth but further its pattern is not consistent in different organs over different life periods. TPPI activity starts to be expressed in the brain at the 10th embryonic day but in most neuronal types it appears at the early infantile period, increases during infancy, reaches high activity levels in the juvenile period and is highest in adult and aged animals. Thus, in mice TPPI activity becomes crucial for the neuronal functions later in development (juvenile period) than in humans and does not decrease with aging. These results are essential as a basis for comparison between normal and pathological TPPI patterns in mice. They can be valuable in view of the use of animal models for studying LINCL and other neurodegenerative disorders.

Serum IgG and IgM ganglioside GM1 antibodies in patients with multiple sclerosis.

INTRODUCTION: In order to obtain more information concerning the pathogenic significance of ganglioside GM1 in multiple sclerosis serum polyclonal IgG and IgM antibodies to GM1 were evaluated in multiple sclerosis patients with relapsing-remitting and secondary progressive forms of the disease. PATIENTS AND METHODS: The evaluated sera were from 55 patients with clinically definite multiple sclerosis and from 20 healthy subjects. Forty-two of patients were with relapsing-remitting and 13 with secondary progressive multiple sclerosis. Antibodies to GM1 were measured using a modification of the enzyme-linked immunosorbent assay technique of Mizutamari et al (1994). RESULTS: A statistically significant difference of serum IgG antibody titres to GM1 was found between the healthy subjects and the multiple sclerosis patients with relapsing-remitting form of the disease (p = 0.04), as well as of serum IgG antibody titres to GM1 between the patients with relapsing-remitting multiple sclerosis in relapse and in remission (p = 0.01). CONCLUSION: Bearing in mind the heterogeneity of multiple sclerosis, the pathogenic significance of serum antibodies to GM1 should be interpreted concerning the precise clinical form of the disease and not the whole group of MS patients. The findings in this study argue for the possible involvement of ganglioside GM1 in the pathogenesis of demyelination in relapsing-remitting multiple sclerosis.