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The effect was accompanied by the prevention of the early hypertrophy of <jats:italic>wobbler<\/jats:italic> neurones, an effect likely due to the promotion of neuronal survival. At the 18th week, <jats:italic>wobbler<\/jats:italic> mice treated with IGF\u2010I + GAGs still showed significantly improved forelimb function, reduced muscle atrophy and a higher number of cervical motor neurones. IGF\u2010I alone and GAGs alone were active up to the 3rd week of treatment; thereafter the beneficial effects of single treatments decreased drastically. GAGs and IGF\u2010I treatments also affected IGF\u2010I plasma and muscle levels. In <jats:italic>wobbler<\/jats:italic> mice there was a progressive reduction in IGF\u2010I plasma levels that was prevented by IGF\u2010I or GAGs alone and greatly increased, even above heterozygote levels, by the combination treatment. Such a powerful increase was correlated by a small enhancement in insulin\u2010like growth factor binding protein\u20103 (IGFBP\u20103) plasma levels, while treatment with IGF\u2010I alone affected very significantly both IGFBP\u20101 and IGFBP\u20103. Co\u2010treatment also prevented the decrease in IGF\u2010I content observed in vehicle\u2010treated <jats:italic>wobbler<\/jats:italic> mice forelimb muscles.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2002.00830.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:59:42Z","timestamp":1047452382000},"page":"194-202","source":"Crossref","is-referenced-by-count":18,"title":["Co\u2010administration of IGF\u2010I and glycosaminoglycans greatly delays motor neurone disease and affects IGF\u2010I expression in the <i>wobbler<\/i> mouse: a long\u2010term study"],"prefix":"10.1111","volume":"81","author":[{"given":"Alfredo","family":"Gorio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Lesma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Madaschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Di Giulio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,3,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970401)48:1<63::AID-JNR6>3.0.CO;2-C"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90766-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.135.6.2358"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"20388","DOI":"10.1016\/S0021-9258(17)32004-5","article-title":"Heparin, heparan sulfate, and dermatan sulfate regulate formation of the insulin\u2010like growth factor\u2010I and insulin\u2010like growth factor\u2010binding protein complexes","volume":"81","author":"Arai T.","year":"1994","journal-title":"J. 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