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Cortical murine neurons lacking the neurofilament light chain protein have an attenuated response to injury in vitro
journal contribution
posted on 2023-05-17, 20:39 authored by Catherine BlizzardCatherine Blizzard, Anna KingAnna King, James VickersJames Vickers, Tracey DicksonTracey DicksonAbstract 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.
History
Publication title
Journal of NeurotraumaVolume
30Issue
22Pagination
1908-1918ISSN
0897-7151Department/School
Menzies Institute for Medical ResearchPublisher
Mary Ann Liebert Inc PublPlace of publication
2 Madison Avenue, Larchmont, USA, Ny, 10538Rights statement
Copyright 2013 Mary Ann LiebertRepository Status
- Restricted