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Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia

Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkin...

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Autores principales: Sawada, Yusuke, Konno, Ayumu, Nagaoka, Jun, Hirai, Hirokazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904196/
https://www.ncbi.nlm.nih.gov/pubmed/27291422
http://dx.doi.org/10.1038/srep27758
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author Sawada, Yusuke
Konno, Ayumu
Nagaoka, Jun
Hirai, Hirokazu
author_facet Sawada, Yusuke
Konno, Ayumu
Nagaoka, Jun
Hirai, Hirokazu
author_sort Sawada, Yusuke
collection PubMed
description Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs.
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spelling pubmed-49041962016-06-14 Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia Sawada, Yusuke Konno, Ayumu Nagaoka, Jun Hirai, Hirokazu Sci Rep Article Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs. Nature Publishing Group 2016-06-13 /pmc/articles/PMC4904196/ /pubmed/27291422 http://dx.doi.org/10.1038/srep27758 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sawada, Yusuke
Konno, Ayumu
Nagaoka, Jun
Hirai, Hirokazu
Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia
title Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia
title_full Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia
title_fullStr Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia
title_full_unstemmed Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia
title_short Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia
title_sort inflammation-induced reversible switch of the neuron-specific enolase promoter from purkinje neurons to bergmann glia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904196/
https://www.ncbi.nlm.nih.gov/pubmed/27291422
http://dx.doi.org/10.1038/srep27758
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