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Cortical murine neurons lacking the neurofilament light chain protein have an attenuated response to injury in vitro

Citation

Blizzard, CA and King, AE and Vickers, J and Dickson, T, Cortical murine neurons lacking the neurofilament light chain protein have an attenuated response to injury in vitro, Journal of Neurotrauma, 30, (22) pp. 1908-1918. ISSN 0897-7151 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 Mary Ann Liebert

DOI: doi:10.1089/neu.2013.2850

Abstract

Abstract Neurofilaments (NFs) have been proposed to have a significant role in attempted axonal regeneration following a variety of forms of injury. The NF triplet proteins of the central nervous system are comprised of light (NF-L), medium (NF-M) and heavy (NF-H) chains and are part of the type IV intermediate filament family. We sought to define the role of NF-L in the neuronal response to trauma and regeneration by examining the effect of total absence of the NF-L protein on neuronal maturation and response to axotomy. This study utilized an in vitro model comprising relatively mature cortical murine neurons derived from either wild-type embryonic (E15) mice or mice with a genetic knockout of NF-L (NF-L KO). Whilst NF-L KO neurons developed to relative maturity at a comparable rate to wild-type control neurons, NF-L KO neurons demonstrated relatively increased expression of α-internexin and decreased expression of NF-M. Further, we demonstrate that α-internexin co-immunoprecipitates with the NF binding protein NDel1 in NFL-KO cortical neurons in vitro. Following localized axotomy, NF-L KO neurons demonstrated reduced amyloid precursor protein accumulation in damaged neurites as well as a significant reduction in the number of axons regenerating (4.79+/-0.58 sprouts) in comparison to control preparations (10.47+/-1.11 sprouts) (p<0.05). These studies indicate that NFs comprising NF-L have a dynamic role in the reactive and regenerative changes in axons following injury.

Item Details

Item Type:Refereed Article
Keywords:axotomy, cytoskeleton, neurofilaments, sprouting, trauma
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Blizzard, CA (Dr Catherine Blizzard)
Author:King, AE (Associate Professor Anna King)
Author:Vickers, J (Professor James Vickers)
Author:Dickson, T (Professor Tracey Dickson)
ID Code:87538
Year Published:2013
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-11-21
Last Modified:2017-11-06
Downloads:0

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