title: [Application of neuronal cell culture in human degenerative brain disorders].
abstract: Neuronal cell culture system has been used for the study of pathochemical evaluations in human degenerative brain disorders, particularly for Krabbe's disease and neuronal ceroid lipofuscinosis. To understand the pathochemistry of Krabbe's disease, we added psychosine into neuronal cell cultures and psychosine treated cells showed the destruction of cytoskeleton and pathy intracellular changes. Electron microscopic finding showed the swelling of the mitochondria. Oligodendrocytes and Schwann cells were isolated from the brains and sciatic nerve of twitcher mouse as an authentic murine model of globoid cell leukodystrophy. Oligodendroglial cells cultured for 22 days were stained by anti-galactocerebroside antibodies. In twitcher oligodendrocyte processes were wirelike and progressively degenerated and there were few membranous expansion. Schwann cells from twitcher could not elongated their processes. These data suggest that psychosine might be important factor to result in these pathological conditions. Furthermore, we studied the effect of protease inhibitors, E-64 on dissociated primary cultures from fetal rat brain. After treated with E-64 in a concentration from 0.1-50 micrograms/ml, numerous cytoplasmic accumulations appeared in neuronal cells. These morphological pictures resemble with those of neuronal ceroid lipofuscinosis, Batten disease. We will discuss the relationship between the deficiency of catepsin H in Batten disease and inclusion bodies found in E-64.
authors.affiliation: Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Eto
authors.forename: H
authors.initials: H
authors.lastname: Ida
authors.forename: K
authors.initials: K
authors.lastname: Matsui
mesh_terms: D000367:Age Factors; D000818:Animals; D056655:Cathepsin H; D002403:Cathepsins / Q000172:deficiency; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007965:Leukodystrophy, Globoid Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D011609:Psychosine / Q000378:metabolism / Q000633:toxicity; D051381:Rats
chemical_list: D011609:Psychosine; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534126:CTSH protein, human; D056655:Cathepsin H; C534127:Ctsh protein, mouse; C534128:Ctsh protein, rat; D007930:Leucine; C024974:E 64