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Cytoskeletal changes during development and aging in the cortex of neurofilament light protein knockout mice

Citation

Liu, Yao and Staal, JA and Canty, AJ and Kirkcaldie, MTK and King, AE and Bibari, O and Mitew, ST and Dickson, TC and Vickers, JC, Cytoskeletal changes during development and aging in the cortex of neurofilament light protein knockout mice, The Journal of Comparative Neurology, 521, (8) pp. 1817-1827. ISSN 0021-9967 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 Wiley Periodicals, Inc.

DOI: doi:10.1002/cne.23261

Abstract

The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprised of the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months and 12 months (5m, 12m) of age, compared with age-matched wild-type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF-P, NF-DP), the medium NF subunit (NFM) and the intermediate filament α-internexin (INT) at P4. At 5 months, NF-DP, NFM and INT remained significantly lower in knockouts. At 12 months, NF-P was again significantly decreased, and INT significantly increased, in knockouts compared to wildtype. In addition, protein levels of class III neuron-specific β-tubulin and microtubule-associated protein 2 (MAP2) were significantly increased in NFL KO mice at P4, 5 months and 12 months, whereas β-actin levels were significantly decreased at P4. Immunocytochemical studies demonstrated that NF-DP accumulated abnormally in the perikarya of cortical neurons by 5 months of age in NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin-immunolabeled non-pyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs.

Item Details

Item Type:Refereed Article
Keywords:neurofilament; cytoskeletal protein; pyramidal neurons; interneuron
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Liu, Yao (Ms Yao Liu)
Author:Staal, JA (Dr Jerome Staal)
Author:Canty, AJ (Associate Professor Alison Canty)
Author:Kirkcaldie, MTK (Dr Matthew Kirkcaldie)
Author:King, AE (Associate Professor Anna King)
Author:Bibari, O (Dr Olivier Bibari)
Author:Mitew, ST (Mr Stanislaw Mitew)
Author:Dickson, TC (Professor Tracey Dickson)
Author:Vickers, JC (Professor James Vickers)
ID Code:82309
Year Published:2012
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-01-24
Last Modified:2017-11-06
Downloads:0

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