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Neuronal Activity and Its Role in Controlling Antioxidant Genes

1
UK Dementia Research Institute, The Medical School, University of Edinburgh, Chancellor’s Building, Edinburgh EH16 4SB, UK
2
Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
3
Centre for Clinical Brain Sciences, University of Edinburgh Chancellor’s Building, Edinburgh, EH16 4SB, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 1933; https://doi.org/10.3390/ijms21061933
Received: 29 January 2020 / Revised: 2 March 2020 / Accepted: 7 March 2020 / Published: 12 March 2020
Forebrain neurons have relatively weak intrinsic antioxidant defenses compared to astrocytes, in part due to hypo-expression of Nrf2, an oxidative stress-induced master regulator of antioxidant and detoxification genes. Nevertheless, neurons do possess the capacity to auto-regulate their antioxidant defenses in response to electrical activity. Activity-dependent Ca2+ signals control the expression of several antioxidant genes, boosting redox buffering capacity, thus meeting the elevated antioxidant requirements associated with metabolically expensive electrical activity. These genes include examples which are reported Nrf2 target genes and yet are induced in a Nrf2-independent manner. Here we discuss the implications for Nrf2 hypofunction in neurons and the mechanisms underlying the Nrf2-independent induction of antioxidant genes by electrical activity. A significant proportion of Nrf2 target genes, defined as those genes controlled by Nrf2 in astrocytes, are regulated by activity-dependent Ca2+ signals in human stem cell-derived neurons. We propose that neurons interpret Ca2+ signals in a similar way to other cell types sense redox imbalance, to broadly induce antioxidant and detoxification genes. View Full-Text
Keywords: neuroprotection; neurodegeneration; oxidative stress; signal transduction; synaptic activity; gene transcription; antioxidants; astrocytes neuroprotection; neurodegeneration; oxidative stress; signal transduction; synaptic activity; gene transcription; antioxidants; astrocytes
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MDPI and ACS Style

Qiu, J.; Dando, O.; Febery, J.A.; Fowler, J.H.; Chandran, S.; Hardingham, G.E. Neuronal Activity and Its Role in Controlling Antioxidant Genes. Int. J. Mol. Sci. 2020, 21, 1933. https://doi.org/10.3390/ijms21061933

AMA Style

Qiu J, Dando O, Febery JA, Fowler JH, Chandran S, Hardingham GE. Neuronal Activity and Its Role in Controlling Antioxidant Genes. International Journal of Molecular Sciences. 2020; 21(6):1933. https://doi.org/10.3390/ijms21061933

Chicago/Turabian Style

Qiu, Jing, Owen Dando, James A. Febery, Jill H. Fowler, Siddharthan Chandran, and Giles E. Hardingham 2020. "Neuronal Activity and Its Role in Controlling Antioxidant Genes" International Journal of Molecular Sciences 21, no. 6: 1933. https://doi.org/10.3390/ijms21061933

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