{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:21:20Z","timestamp":1790043680526,"version":"4.0.1"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T00:00:00Z","timestamp":1341532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>M. Kuronen, M. Hermansson, O. Manninen, I. Zech, M. Talvitie, T. Laitinen, O. Gr\u00f6hn, P. Somerharju, M. Eckhardt, J. D. Cooper, A.\u2010E. Lehesjoki, U. Lahtinen and O. Kopra (2012) <jats:italic>Neuropathology and Applied Neurobiology<\/jats:italic><jats:bold>38,<\/jats:bold> 471\u2013486<\/jats:p><jats:p><jats:bold>Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model <jats:italic>Cln8<jats:sup>mnd<\/jats:sup><\/jats:italic>: implications to delayed myelination and oligodendrocyte maturation<\/jats:bold><\/jats:p><jats:p><jats:bold>Aims:<\/jats:bold>\n          <jats:italic>CLN8<\/jats:italic> deficiency underlies one of a group of devastating childhood neurodegenerative disorders, the neuronal ceroid lipofuscinoses. The function of the CLN8 protein is currently unknown, but a role in lipid metabolism has been proposed. In human CLN8 diseased brains, alterations in lipid composition have been detected. To further investigate the connection of CLN8 to lipid metabolism, we characterized the lipid composition of early symptomatic <jats:italic>Cln8<\/jats:italic>\u2010deficient mouse (<jats:italic>Cln8<jats:sup>mnd<\/jats:sup><\/jats:italic>) brains. <jats:bold>Methods:<\/jats:bold> For lipid profiling, <jats:italic>Cln8<jats:sup>mnd<\/jats:sup><\/jats:italic> cerebral cortical tissue was analysed by liquid chromatography\/mass spectrometry. Galactolipid synthesis was measured through enzyme activity and real\u2010time mRNA expression analyses. Based on the findings, myelination and white matter integrity were studied by immunohistochemistry, stereological methods, electron microscopy and magnetic resonance imaging. The development of myelin\u2010forming oligodendrocytes was also studied <jats:italic>in vitro<\/jats:italic>. <jats:bold>Results:<\/jats:bold> Sphingolipid profiling showed a selective reduction in myelin\u2010enriched galactolipids. The mRNA expression and activity of UDP\u2010galactose:ceramide galactosyltransferase (CGT), the key enzyme in the galactolipid synthesis, was reduced in the <jats:italic>Cln8<jats:sup>mnd<\/jats:sup><\/jats:italic> brain. Expression of oligodendrocyte markers suggests a maturation defect. The amount of myelin was reduced in 1\u2010month\u2010old <jats:italic>Cln8<jats:sup>mnd<\/jats:sup><\/jats:italic> mice, but reached normal levels by 5 months of age. The level of <jats:italic>Cln8<\/jats:italic> gene expression followed the developmental pattern of myelin formation and was high in primary oligodendrocytes. <jats:bold>Conclusions:<\/jats:bold> Taken together, these observations suggest that galactolipid deficiency and delayed myelin maturation characterize the early CLN8 disease pathogenesis through a maturation defect of oligodendrocytes.<\/jats:p>","DOI":"10.1111\/j.1365-2990.2011.01233.x","type":"journal-article","created":{"date-parts":[[2011,11,2]],"date-time":"2011-11-02T08:34:53Z","timestamp":1320222893000},"page":"471-486","source":"Crossref","is-referenced-by-count":18,"title":["Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model <i>Cln8<sup>mnd<\/sup><\/i>: implications to delayed myelination and oligodendrocyte maturation"],"prefix":"10.1111","volume":"38","author":[{"given":"M.","family":"Kuronen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hermansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Manninen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Zech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Talvitie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Laitinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Gr\u00f6hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Somerharju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Eckhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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