title: Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice.
abstract: Cathepsin K is important for the brain, because its deficiency in mice is associated with a marked decrease in differentiated astrocytes and changes in neuronal patterning in the hippocampus as well as with learning and memory deficits. As cathepsin K activity is most prominent in hippocampal regions of wild type animals, we hypothesised alterations in astrocyte-mediated support of neurons as a potential mechanism underlying the impaired brain functions in cathepsin K-deficient mice. To address this hypothesis, we have generated and characterised astroglia-rich primary cell cultures from cathepsin K-deficient and wild type mice and compared these cultures for possible changes in metabolic support functions and cell composition. Interestingly, cells expressing the oligodendrocytic markers myelin-associated glycoprotein and myelin basic protein were more frequent in astroglia-rich cultures from cathepsin K-deficient mice. However, cell cultures from both genotypes were morphologically comparable and similar with respect to glucose metabolism. In addition, specific glutathione content, glutathione export and γ-glutamyl-transpeptidase activity remained unchanged, whereas the specific activities of glutathione reductase and glutathione-S-transferase were increased by around 50% in cathepsin K-deficient cultures. Thus, lack of cathepsin K in astroglia-rich cultures appears not to affect metabolic supply functions of astrocytes but to facilitate the maturation of oligodendrocytes.
authors.affiliation: School of Engineering and Science, Research Center MOLIFE, Molecular Life Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dauth
authors.forename: Maike M
authors.initials: MM
authors.lastname: Schmidt
authors.forename: Maren
authors.initials: M
authors.lastname: Rehders
authors.forename: Frank
authors.initials: F
authors.lastname: Dietz
authors.forename: Sørge
authors.initials: S
authors.lastname: Kelm
authors.forename: Ralf
authors.initials: R
authors.lastname: Dringen
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D056657:Cathepsin K / Q000172:deficiency* / Q000378:metabolism; D018929:Cell Culture Techniques; D005260:Female; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
chemical_list: D056657:Cathepsin K; D005978:Glutathione; D005947:Glucose