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Glycobiology Advance Access published online on May 14, 2008

Glycobiology, doi:10.1093/glycob/cwn032
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Impaired hypoglossal nerve regeneration in the mutant mice lacking complex gangliosides: down-regulation of neurotrophic factors and receptors as possible mechanisms

Daiji Kittaka1,*, Michi-ichirou Itoh2,*, Yuhsuke Ohmi1, Yuji Kondo1, Satoshi Fukumoto1, Takeshi Urano1, Orie Tajima1,3, Keiko Furukawa1,3 and Koichi Furukawa1,4

1 Department of Biochemistry II, Graduate School of Medicine, Nagoya University School of Medicine, Nagoya 466-0065
2 Department of Oral and Maxillofacial Surgery, Nagasaki 852-8102
3 Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan


4 To whom reprint requests should be addressed: Koichi Furukawa at Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 Japan, Tel: 81-52-744-2070; Fax: 81-52-744-2069; E-mail: koichi{at}med.nagoya-u.ac.jp

Received on February 29, 2008; accepted on April 21, 2008

Gangliosides, sialic acid-containing glycosphingolipids, have been considered to play roles as neurotrophic factors. Exogenous gangliosides added to 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 number of surviving neurons and 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.

Key words: gangliosides / hypoglossal nerve / knockout / regeneration / neurotrophic factor / neuron


* These authors equally contributed in this study.


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