Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro

Ng, Jian Ming Jeremy, Chen, Minghui Jessica, Leung, Jacqueline Y. K., Peng, Zhao Feng, Manikandan, Jayapal, Qi, Robert Z., Chuah, Meng Inn, West, Adrian K., Vickers, James C., Lu, Jia, Cheung, Nam Sang and Chung, Roger S. 2012, Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro, Journal of cellular and molecular medicine, vol. 16, no. 4, pp. 789-811.

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Title Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro
Author(s) Ng, Jian Ming Jeremy
Chen, Minghui Jessica
Leung, Jacqueline Y. K.
Peng, Zhao Feng
Manikandan, Jayapal
Qi, Robert Z.
Chuah, Meng Inn
West, Adrian K.
Vickers, James C.
Lu, Jia
Cheung, Nam Sang
Chung, Roger S.
Journal name Journal of cellular and molecular medicine
Volume number 16
Issue number 4
Start page 789
End page 811
Total pages 23
Publisher Wiley - Blackwell Publishing
Place of publication Oxford, England
Publication date 2012-04
ISSN 1582-1838
1582-4934
Keyword(s) neurons
axotomy
microarray
regeneration
neurite cytoskeleton
secondary processes
Summary 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.
Language eng
Field of Research 069999 Biological Sciences not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2011, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30046912

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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