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Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro

journal contribution
posted on 2023-05-17, 11:36 authored by Ng, JMJ, Chen, MJ, Jacqueline LeungJacqueline Leung, Peng, ZF, Manikandan, J, Qi, RZ, Meng Inn ChuahMeng Inn Chuah, Adrian WestAdrian West, James VickersJames Vickers, Lu, J, Cheung, NS, Chung, RS
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.

History

Publication title

Journal of Cellular and Molecular Medicine

Volume

16

Issue

4

Pagination

789-811

ISSN

1582-4934

Department/School

Menzies Institute for Medical Research

Publisher

Wiley - Blackwell Publishing Ltd.

Place of publication

The Atrium, Chichester, West Sussex PO19 8SQ, UK

Rights statement

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

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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