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Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro

Citation

Ng, JMJ and Chen, MJ and Leung, JYK and Peng, ZF and Manikandan, J and Qi, RZ and Chuah, MI and West, AK and Vickers, JC and Lu, J and Cheung, NS and Chung, RS, Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro, Journal of Cellular and Molecular Medicine, 16, (4) pp. 789-811. ISSN 1582-4934 (2012) [Refereed Article]


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Copyright Statement

Copyright 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

DOI: doi:10.1111/j.1582-4934.2011.01361.x

Abstract

Axotomized neurons have the innate ability to undergo regenerative sprouting but this is often impeded by the inhibitory central nervous system environment. To gain mechanistic insights into the key molecular determinates that specifically underlie neuronal regeneration at a transcriptomic level, we have undertaken a DNA microarray study on mature cortical neuronal clusters maintained in vitro at 8, 15, 24 and 48 hrs following complete axonal severance. A total of 305 genes, each with a minimum fold change of 1.5 for at least one out of the four time points and which achieved statistical significance (one-way ANOVA, P  0.05), were identified by DAVID and classified into 14 different functional clusters according to Gene Ontology. From our data, we conclude that post-injury regenerative sprouting is an intricate process that requires two distinct pathways. Firstly, it involves restructuring of the neurite cytoskeleton, determined by compound actin and microtubule dynamics, protein trafficking and concomitant modulation of both guidance cues and neurotrophic factors. Secondly, it elicits a cell survival response whereby genes are regulated to protect against oxidative stress, inflammation and cellular ion imbalance. Our data reveal that neurons have the capability to fight insults by elevating biological antioxidants, regulating secondary messengers, suppressing apoptotic genes, controlling ion-associated processes and by expressing cell cycle proteins that, in the context of neuronal injury, could potentially have functions outside their normal role in cell division. Overall, vigilant control of cell survival responses against pernicious secondary processes is vital to avoid cell death and ensure successful neurite regeneration.

Item Details

Item Type:Refereed Article
Keywords:Aurora kinase, neurons, axotomy, microarray, regeneration, neurite cytoskeleton, secondary processes
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:Ng, JMJ (Mr Jeremy Ng)
Author:Chen, MJ (Ms Minghui Chen)
Author:Leung, JYK (Dr Jacqueline Leung)
Author:Chuah, MI (Dr Inn Chuah)
Author:West, AK (Professor Adrian West)
Author:Vickers, JC (Professor James Vickers)
Author:Cheung, NS (Dr Nam Cheung)
Author:Chung, RS (Associate Professor Roger Chung)
ID Code:77582
Year Published:2012
Web of Science® Times Cited:2
Deposited By:Medicine (Discipline)
Deposited On:2012-05-04
Last Modified:2015-01-21
Downloads:1 View Download Statistics

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