Transcriptional insights on the regenerative mechanics of axotomized neurons in vitro
Jian Ming Jeremy Ng
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Both the authors contributed equally to this study.
Search for more papers by this authorMinghui Jessica Chen
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Both the authors contributed equally to this study.
Search for more papers by this authorJacqueline Y.K. Leung
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorZhao Feng Peng
Key Laboratory of Biogeology and Environmental Geology of the Ministry of Education, China University of Geosciences, Wuhan, China
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Search for more papers by this authorJayapal Manikandan
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Search for more papers by this authorRobert Z. Qi
Department of Biochemistry, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
Search for more papers by this authorMeng Inn Chuah
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorAdrian K. West
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorJames C. Vickers
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorJia Lu
Defense Medical and Environmental Research Institute, DSO National Laboratories, National University of Singapore, Singapore
Search for more papers by this authorCorresponding Author
Nam Sang Cheung
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
School of Life and Environmental Sciences, Deakin University, Burwood, Melbourne, Australia
Roger S. CHUNG, Steve Nam Sang CHEUNG, Menzies Research Institute, School of Medicine Private Bag 23, University of Tasmania, Hobart, Tasmania 7001, Australia. Tel.: +613-6226 2657/2710 Fax: +613 6226 7704 E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Roger S. Chung
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Roger S. CHUNG, Steve Nam Sang CHEUNG, Menzies Research Institute, School of Medicine Private Bag 23, University of Tasmania, Hobart, Tasmania 7001, Australia. Tel.: +613-6226 2657/2710 Fax: +613 6226 7704 E-mail: [email protected], [email protected]Search for more papers by this authorJian Ming Jeremy Ng
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Both the authors contributed equally to this study.
Search for more papers by this authorMinghui Jessica Chen
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Both the authors contributed equally to this study.
Search for more papers by this authorJacqueline Y.K. Leung
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorZhao Feng Peng
Key Laboratory of Biogeology and Environmental Geology of the Ministry of Education, China University of Geosciences, Wuhan, China
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Search for more papers by this authorJayapal Manikandan
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Search for more papers by this authorRobert Z. Qi
Department of Biochemistry, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
Search for more papers by this authorMeng Inn Chuah
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorAdrian K. West
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorJames C. Vickers
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Search for more papers by this authorJia Lu
Defense Medical and Environmental Research Institute, DSO National Laboratories, National University of Singapore, Singapore
Search for more papers by this authorCorresponding Author
Nam Sang Cheung
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
School of Life and Environmental Sciences, Deakin University, Burwood, Melbourne, Australia
Roger S. CHUNG, Steve Nam Sang CHEUNG, Menzies Research Institute, School of Medicine Private Bag 23, University of Tasmania, Hobart, Tasmania 7001, Australia. Tel.: +613-6226 2657/2710 Fax: +613 6226 7704 E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Roger S. Chung
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Roger S. CHUNG, Steve Nam Sang CHEUNG, Menzies Research Institute, School of Medicine Private Bag 23, University of Tasmania, Hobart, Tasmania 7001, Australia. Tel.: +613-6226 2657/2710 Fax: +613 6226 7704 E-mail: [email protected], [email protected]Search for more papers by this authorAbstract
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.
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