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

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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 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.

Original languageEnglish (US)
Pages (from-to)12028-12037
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number35
DOIs
StatePublished - Aug 29 2012

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Sodium-Calcium Exchanger
Axons
Actins
Reactive Oxygen Species
Oxidative Stress
Nervous System Diseases
Pathology
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "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",
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 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.",
author = "Anna Bell and Michael Forte and Dennis Bourdette",
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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 - Bell, Anna

AU - Forte, Michael

AU - Bourdette, Dennis

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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