TY - JOUR
T1 - Focal increases of axoplasmic Ca 2+, aggregation of sodium-calcium exchanger, N-type Ca 2+ channel, and actin define the sites of spheroids in axons undergoing oxidative stress
AU - Barsukova, Anna G.
AU - Forte, Michael
AU - Bourdette, Dennis
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/8/29
Y1 - 2012/8/29
N2 - 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 a1B 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.
AB - 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 a1B 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.
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U2 - 10.1523/JNEUROSCI.0408-12.2012
DO - 10.1523/JNEUROSCI.0408-12.2012
M3 - Article
C2 - 22933787
AN - SCOPUS:84865448921
SN - 0270-6474
VL - 32
SP - 12028
EP - 12037
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 35
ER -