Glycobiology Advance Access originally published online on May 14, 2008
Glycobiology 2008 18(7):509-516; doi:10.1093/glycob/cwn032
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Impaired hypoglossal nerve regeneration in mutant mice lacking complex gangliosides: Down-regulation of neurotrophic factors and receptors as possible mechanisms
3 Department of Biochemistry II, Graduate School of Medicine, Nagoya University School of Medicine, Nagoya 466-0065
4 Department of Oral and Maxillofacial Surgery, Nagasaki 852-8102
5 Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan
1 To whom correspondence should be addressed: Tel: +81-52-744-2070; Fax: +81-52-744-2069; e-mail: koichi{at}med.nagoya-u.ac.jp
Received on February 29, 2008; revised on April 19, 2008; accepted on April 21, 2008
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.
Key words: gangliosides / hypoglossal nerve / knockout / regeneration / neurotrophic factor
2 These authors equally contributed in this study.