{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:22:32Z","timestamp":1790043752246,"version":"4.0.1"},"reference-count":37,"publisher":"Society for Neuroscience","issue":"34","license":[{"start":{"date-parts":[[2008,2,22]],"date-time":"2008-02-22T00:00:00Z","timestamp":1203638400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,8,22]]},"abstract":"<jats:p>Metachromatic leukodystrophy is a lysosomal storage disorder caused by deficiency in the sulfolipid degrading enzyme arylsulfatase A (ASA). In the absence of a functional ASA gene, 3-<jats:italic>O<\/jats:italic>-sulfogalactosylceramide (sulfatide; SGalCer) and other sulfolipids accumulate. The storage is associated with progressive demyelination and various finally lethal neurological symptoms. Lipid storage, however, is not restricted to myelin-producing cells but also occurs in neurons. It is unclear whether neuronal storage contributes to symptoms of the patients. Therefore, we have generated transgenic ASA-deficient [ASA(\u2212\/\u2212)] mice overexpressing the sulfatide synthesizing enzymes UDP-galactose:ceramide galactosyltransferase (CGT) and cerebroside sulfotransferase (CST) in neurons to provoke neuronal lipid storage. CGT-transgenic ASA(\u2212\/\u2212) [CGT\/ASA(\u2212\/\u2212)] mice showed an accumulation of C18:0 fatty acid-containing SGalCer in the brain. Histochemically, an increase in sulfolipid storage could be detected in central and peripheral neurons of both CGT\/ASA(\u2212\/\u2212) and CST\/ASA(\u2212\/\u2212) mice compared with ASA(\u2212\/\u2212) mice. CGT\/ASA(\u2212\/\u2212) mice developed severe neuromotor coordination deficits and weakness of hindlimbs and forelimbs. Light and electron microscopic analyses demonstrated nerve fiber degeneration in the spinal cord of CGT\/ASA(\u2212\/\u2212) mice. CGT\/ASA(\u2212\/\u2212) and, to a lesser extent, young ASA(\u2212\/\u2212) mice exhibited cortical hyperexcitability, with recurrent spontaneous cortical EEG discharges lasting 5\u201315 s. These observations suggest that SGalCer accumulation in neurons contributes to disease phenotype.<\/jats:p>","DOI":"10.1523\/jneurosci.2329-07.2007","type":"journal-article","created":{"date-parts":[[2007,8,22]],"date-time":"2007-08-22T16:23:49Z","timestamp":1187799829000},"page":"9009-9021","source":"Crossref","is-referenced-by-count":66,"title":["Sulfatide Storage in Neurons Causes Hyperexcitability and Axonal Degeneration in a Mouse Model of Metachromatic Leukodystrophy"],"prefix":"10.1523","volume":"27","author":[{"given":"Matthias","family":"Eckhardt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin Khalaj","family":"Hedayati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julika","family":"Pitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"L\u00fcllmann-Rauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Ngamli","family":"Fewou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkmar","family":"Gieselmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,8,22]]},"reference":[{"key":"2023041303270353000_27.34.9009.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1982.tb10875.x"},{"key":"2023041303270353000_27.34.9009.2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970331)69:3<335::AID-AJMG22>3.0.CO;2-R"},{"key":"2023041303270353000_27.34.9009.3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.18.11.1140"},{"key":"2023041303270353000_27.34.9009.4","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007010205037"},{"key":"2023041303270353000_27.34.9009.5","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.8.2514"},{"key":"2023041303270353000_27.34.9009.6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706947"},{"key":"2023041303270353000_27.34.9009.7","doi-asserted-by":"publisher","DOI":"10.1021\/bi00591a005"},{"key":"2023041303270353000_27.34.9009.8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s004010000318","article-title":"Morphological alterations in the inner ear of the arylsulfatase A-deficientmouse","volume":"101","author":"Coenen","year":"2001","journal-title":"Acta Neuropathol (Berl)"},{"key":"2023041303270353000_27.34.9009.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02085-5"},{"key":"2023041303270353000_27.34.9009.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00647-3"},{"key":"2023041303270353000_27.34.9009.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02374-5"},{"key":"2023041303270353000_27.34.9009.12","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20020946"},{"key":"2023041303270353000_27.34.9009.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03221.x"},{"key":"2023041303270353000_27.34.9009.14","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005471106088"},{"key":"2023041303270353000_27.34.9009.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14821"},{"key":"2023041303270353000_27.34.9009.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05195.x"},{"key":"2023041303270353000_27.34.9009.17","unstructured":"Kolodny EH Fluharty AL (1995) in The metabolic and molecular bases of inherited disease, Metachromatic leukodystrophy and multiple sulfatase deficiency: sulfatide lipidosis, eds Scriver CR Beaudet AL Sly WS Valle D (McGraw-Hill, New York), pp 2693\u20132739."},{"key":"2023041303270353000_27.34.9009.18","doi-asserted-by":"publisher","DOI":"10.1016\/0736-5748(96)81215-9"},{"key":"2023041303270353000_27.34.9009.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-004-0708-3"},{"key":"2023041303270353000_27.34.9009.20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s004180100286","article-title":"Lysosomal sulfoglycolipid storage in the kidneys of mice deficient for arylsulfatase A (ASA) and of double-knockout mice deficient for ASA and galactosylceramide synthase","volume":"116","author":"L\u00fcllmann-Rauch","year":"2001","journal-title":"Histochem Cell Biol"},{"key":"2023041303270353000_27.34.9009.21","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1523\/JNEUROSCI.17-12-04688.1997","article-title":"Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation","volume":"17","author":"L\u00fcthi","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303270353000_27.34.9009.22","doi-asserted-by":"publisher","DOI":"10.1023\/B:NEUR.0000046572.53905.2c"},{"key":"2023041303270353000_27.34.9009.23","doi-asserted-by":"publisher","DOI":"10.1021\/bi00830a008"},{"key":"2023041303270353000_27.34.9009.24","doi-asserted-by":"crossref","unstructured":"Norton WT Cammer W (1984) in Myelin, Chemical pathology of diseases involving myelin, ed Morell P (Plenum, New York), pp 147\u2013195.","DOI":"10.1007\/978-1-4757-1830-0_5"},{"key":"2023041303270353000_27.34.9009.25","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10264"},{"key":"2023041303270353000_27.34.9009.26","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0021-9258(19)45614-7","article-title":"Ceramide galactoside of enriched neuronal and glial fractions from rat brain","volume":"247","author":"Raghavan","year":"1972","journal-title":"J Biol Chem"},{"key":"2023041303270353000_27.34.9009.27","unstructured":"Sambrook J Fritsch EF Maniatis T (1989) Molecular cloning: a laboratory manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY)."},{"key":"2023041303270353000_27.34.9009.28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110641200"},{"key":"2023041303270353000_27.34.9009.29","doi-asserted-by":"publisher","DOI":"10.1007\/s004280000360"},{"key":"2023041303270353000_27.34.9009.30","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199906000-00009"},{"key":"2023041303270353000_27.34.9009.31","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1399-0004.1996.tb02376.x","article-title":"Late juvenile metachromatic leukodystrophy (MLD) in three patients with a similar clinical course and identical mutation on one allele","volume":"50","author":"Tylki-Szymanska","year":"1996","journal-title":"Clin Genet"},{"key":"2023041303270353000_27.34.9009.32","doi-asserted-by":"crossref","unstructured":"van der Putten H Wiederhold KH Probst A Barbieri S Mistl C Danner S Kauffmann S Hofele K Spooren WP Rueg MA Lin S Caroni P Sommer B Tolnay M Bilbe G (2000) Neuropathology in mice expressing human \u03b1-synuclein. J Neurosci, 6021\u20136029.","DOI":"10.1523\/JNEUROSCI.20-16-06021.2000"},{"key":"2023041303270353000_27.34.9009.33","unstructured":"von Figura K Gieselmann V Jaeken J (2001) in The metabolic and molecular basis of inherited disease, Metachromatic leukodystrophy, eds Scriver CR Beaudet AL Valle D Sly WS (McGraw-Hill, New York), pp 3695\u20133724."},{"key":"2023041303270353000_27.34.9009.34","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0883-6"},{"key":"2023041303270353000_27.34.9009.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03891.x"},{"key":"2023041303270353000_27.34.9009.36","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(85)90447-6"},{"key":"2023041303270353000_27.34.9009.37","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20230"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2329-07.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T18:11:35Z","timestamp":1681409495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2329-07.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,22]]},"references-count":37,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2007,8,22]]},"published-print":{"date-parts":[[2007,8,22]]}},"alternative-id":["10.1523\/JNEUROSCI.2329-07.2007"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2329-07.2007","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,22]]}}}