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 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
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