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Calcineurin Signaling Mediates Disruption of the Axon Initial Segment Cytoskeleton after Injury

Authors :
Yanan Zhao
Xuanyuan Wu
Xin Chen
Jianan Li
Cuiping Tian
Jiangrui Chen
Cheng Xiao
Guisheng Zhong
Shuijin He
Source :
iScience, Vol 23, Iss 2, Pp - (2020)
Publication Year :
2020
Publisher :
Elsevier, 2020.

Abstract

Summary: The axon initial segment (AIS) cytoskeleton undergoes rapid and irreversible disruption prior to cell death after injury, and loss of AIS integrity can produce profound neurological effects on the nervous system. Here we described a previously unrecognized mechanism for ischemia-induced alterations in AIS integrity. We show that in hippocampal CA1 pyramidal neurons Nav1.6 mostly preserves at the AIS after disruption of the cytoskeleton in a mouse model of middle cerebral artery occlusion. Genetic removal of neurofascin-186 leads to rapid disruption of Nav1.6 following injury, indicating that neurofascin is required for Nav1.6 maintenance at the AIS after cytoskeleton collapse. Importantly, calcineurin inhibition with FK506 fully protects AIS integrity and sufficiently prevents impairments of spatial learning and memory from injury. This study provides evidence that calcineurin activation is primarily involved in initiating disassembly of the AIS cytoskeleton and that maintaining AIS integrity is crucial for therapeutic strategies to facilitate recovery from injury. : Neuroscience; Molecular Neuroscience; Cellular Neuroscience Subject Areas: Neuroscience, Molecular Neuroscience, Cellular Neuroscience

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
25890042
Volume :
23
Issue :
2
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.23a847f613224a59842dd4e4b073a7ae
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2020.100880