Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice

László Siklös, József I. Engelhardt, Maria E. Alexianu, Mark E. Gurney, Teepu Siddique, Stanley H. Appel

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Transgenic mice with Cu,Zn superoxide dismutase (SOD-1) mutations provide a unique model to examine altered Ca homeostasis in selectively vulnerable and resistant motoneurons. In degenerating spinal motoneurons of G93 A SOD-I mice, developing vacuoles were filled with calcium, while calcium was gradually depleted from the cytoplasm and intact mitochondria. In oculomotor neurons, no degenerative changes, vacuolization, or increased calcium were noted. Motor axon terminals of interosseus muscle gradually degenerated and intracellular calcium was depleted. Oculomotor terminals of mutant SOD-1 mice were smaller and exhibited no degenerative changes, but did exhibit unique membrane-enclosed organelles containing calcium. Spinal motoneurons of SOD-1 mice were shown to have fewer calcium binding proteins, such as parvalbumin, compared with oculomotor neurons. These data suggest that the SOD-1 mutation is associated with impaired calcium homeostasis in motoneurons in vivo, with increased likelihood of degeneration associated with higher levels of intracellular calcium and lower to absent levels of calbindin-D28K and/or parvalbumin, and decreased likelihood of degeneration associated with minimally changed calcium and ample calbindin-D28K and/or parvalbumin.

Original languageEnglish
Pages (from-to)571-587
Number of pages17
JournalJournal of Neuropathology and Experimental Neurology
Volume57
Issue number6
DOIs
Publication statusPublished - Jun 1998

Keywords

  • Calcium
  • Calcium-binding proteins
  • Motoneuron
  • Neurodegeneration
  • Oxidative stress
  • SOD-1
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice'. Together they form a unique fingerprint.

  • Cite this