title: Impaired hypoglossal nerve regeneration in mutant mice lacking complex gangliosides: down-regulation of neurotrophic factors and receptors as possible mechanisms.
abstract: Gangliosides, sialic acid-containing glycosphingolipids, have been considered to play roles as neurotrophic factors. Exogenous gangliosides added to the culture medium of neuronal cells or injected in artificially injured sites of nerve tissues actually showed neurotrophic factor-like effects such as neurite extension and alleviation of nerve tissue deterioration. In this study, neuroregeneration in the mutant mice lacking complex gangliosides was examined. To determine whether the nervous system maintains regenerative activity in the long-term absence of complex gangliosides, we analyzed hypoglossal nerve regeneration after axotomy in the mutant mice of GM2/GD2 synthase. These mice exhibited marked impairment of regenerative activity both in the number of surviving neurons and in the number of peroxidase-positive neurons. Moreover, reduced levels of gene expression of neurotrophic factors and their receptors including CNTF, p75 NTR, TrkB, and others in hypoglossal neurons were observed in real-time reverse transcription-polymerase chain reaction combined with laser capture microdissection, suggesting that these molecules are, at least partly, involved in the regeneration of lesioned nerves and that their expression levels are precisely controlled in the presence of intact expression of complex gangliosides.
authors.affiliation: Department of Biochemistry II, Graduate School of Medicine, Nagoya University School of Medicine, Nagoya 466-0065, Japan.
authors.forename: Daiji
authors.initials: D
authors.lastname: Kittaka
authors.forename: Michi-ichirou
authors.initials: M
authors.lastname: Itoh
authors.forename: Yuhsuke
authors.initials: Y
authors.lastname: Ohmi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kondo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Orie
authors.initials: O
authors.lastname: Tajima
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis; D015536:Down-Regulation; D005732:Gangliosides / Q000096:biosynthesis* / Q000235:genetics; D007002:Hypoglossal Nerve / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009416:Nerve Regeneration; D020813:Receptor, trkB / Q000096:biosynthesis; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis
chemical_list: D020934:Ciliary Neurotrophic Factor; D005732:Gangliosides; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D020813:Receptor, trkB