Intracellular Calcium Parallels Motoneuron Degeneration in SOD-1 Mutant Mice

• Published in: Journal of neuropathology and experimental neurology 1998-06, Vol.57 (6), p.571-587
• Main Authors: Siklós, László, Engelhardt, József I, Alexianu, Maria E, Gurney, Mark E, Siddique, Teepu, Appel, Stanley H
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antimony; Biological and medical sciences; Calcium - analysis; Calcium - metabolism; Calcium binding proteins; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Histocytochemistry - methods; Homeostasis - physiology; Humans; Medical sciences; Mice; Mice, Transgenic; Microscopy, Electron; Motor Neurons - chemistry; Motor Neurons - enzymology; Motor Neurons - ultrastructure; Muscle, Skeletal - innervation; Mutagenesis - physiology; Nerve Degeneration - metabolism; Neurology; Oculomotor Muscles - innervation; Oculomotor Nerve - chemistry; Oculomotor Nerve - cytology; Oxalates; Parvalbumins - analysis; Presynaptic Terminals - pathology; Protein binding; Spinal Cord - chemistry; Spinal Cord - pathology; Superoxide Dismutase - genetics; Superoxides; Vacuoles - ultrastructure; Zinc compounds
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199806000-00005

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-1 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.