Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice

L. Siklós, J. 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
Publication statusPublished - Jun 1998

Fingerprint

Motor Neurons
Calcium
Parvalbumins
Calbindin 1
Homeostasis
Neurons
Mutation
Calcium-Binding Proteins
Presynaptic Terminals
Vacuoles
Organelles
Transgenic Mice
Mitochondria
Cytoplasm
Muscles
Membranes

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice. / Siklós, L.; Engelhardt, J.; Alexianu, Maria E.; Gurney, Mark E.; Siddique, Teepu; Appel, Stanley H.

In: Journal of Neuropathology and Experimental Neurology, Vol. 57, No. 6, 06.1998, p. 571-587.

Research output: Contribution to journalArticle

Siklós, L. ; Engelhardt, J. ; Alexianu, Maria E. ; Gurney, Mark E. ; Siddique, Teepu ; Appel, Stanley H. / Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice. In: Journal of Neuropathology and Experimental Neurology. 1998 ; Vol. 57, No. 6. pp. 571-587.
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