Sulfatide accumulation in the dystrophic terminals of gracile axonal dystrophy mice: Lipid analysis using matrix-assisted laser desorption/ionization imaging mass spectrometry

Sayoko Onishi, Yoshiki Tatsumi, Keiji Wada, Hyun Jeong Yang, Yuki Sugiura, Mitsutoshi Setou, Hiroo Yoshikawa

Research output: Contribution to journalArticle

6 Citations (Scopus)


The gracile axonal dystrophy (gad) mutation in Uch-l1, the gene encoding the ubiquitin carboxy-terminal hydrolase isozyme L1 (UCH-L1), causes selective dying back degeneration of dorsal root ganglion neuron in the medulla oblongata along with progressive sensory-motor ataxia. Axonal spheroids are observed within degenerating axons, and their contents may illuminate the pathogenic mechanisms leading to neurodegeneration in gad mice. To analyze changes in negatively charged lipid molecules in dystrophic axons of gad mice, we performed matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS), electron microscopy, and fluorescence immunohistochemistry on tissue sections from gad and wild-type mouse medulla. MALDI-IMS revealed that m/z 806.68 and 822.68 molecules, assigned to sulfatide (ST) C18:0 and ST C18:0(OH), respectively, were concentrated in the dorsomedial medulla. This spatial distribution overlapped significantly with that of axonal spheroids. Immunostaining revealed that spheroids accumulated myelin and lymphocyte protein, a known ST binding protein. Sulfatides with short-chain fatty acids (C16-C20) are generally localized in intracellular vesicles; therefore, ST C18:0 accumulation may reflect intracellular vesicle aggregation within spheroids. Ubiquitin system disruption apparently alters lipid metabolism, membrane organization, protein turnover, and axonal transport. Changes in membrane organization, particularly STs within lipid rafts, may disrupt cellular signaling pathways necessary for neuronal viability.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalMedical Molecular Morphology
Issue number3
Publication statusPublished - 2013 Sep 1



  • Electron microscopy
  • Fluorescence immunohistochemistry
  • Gracile axonal dystrophy mice
  • Matrix-assisted laser desorption/ionization imaging mass spectrometry
  • Spheroid
  • Sulfatide accumulation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology

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