title: Focal increases of axoplasmic Ca2+, aggregation of sodium-calcium exchanger, N-type Ca2+ channel, and actin define the sites of spheroids in axons undergoing oxidative stress.
abstract: Axonal spheroids occur as part of the pathology of a variety of neurologic diseases. Reactive oxygen species (ROS) trigger formation of spheroids, axonal severing, and Ca(2+) overload. The mechanisms by which ROS lead to the spheroid formation at specific axonal sites remain elusive. Here, using adult mouse primary neurons, we investigate the role of Ca(2+), its regulating systems, and cytoskeletal changes in formation of axonal spheroids triggered by ROS. The results reveal that dramatically higher axoplasmic Ca(2+) levels occur at the sites of axonal spheroids than in the rest of the axon. High focal axoplasmic Ca(2+) levels correlate with focal aggregation of the reverse Na(+)/Ca(2+) exchanger 1, voltage-gated N-type Ca(2+) channel α1B subunit, and actin at the sites of spheroids in individual axons. This study provides new insights into the mechanism of a spheroid formation at specific sites along axons undergoing oxidative stress and a basis for new neuroprotective strategies.
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239, USA. barsukov@ohsu.edu
authors.forename: Anna G
authors.initials: AG
authors.lastname: Barsukova
authors.forename: Michael
authors.initials: M
authors.lastname: Forte
authors.forename: Dennis
authors.initials: D
authors.lastname: Bourdette
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000199:Actins; D020864:Calcium Channels, N-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium