Characterisation of the expression of NMDA receptors in human astrocytes.

Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable of responding to endogenous neurotransmitters has resulted in the need to reassess astrocytic p...

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Autores principales:	Ming-Chak Lee, Ka Ka Ting, Seray Adams, Bruce J Brew, Roger Chung, Gilles J Guillemin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6615200495244446b1a7e848f5274e08
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spelling	oai:doaj.org-article:6615200495244446b1a7e848f5274e082021-11-18T07:02:20ZCharacterisation of the expression of NMDA receptors in human astrocytes.1932-620310.1371/journal.pone.0014123https://doaj.org/article/6615200495244446b1a7e848f5274e082010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21152063/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable of responding to endogenous neurotransmitters has resulted in the need to reassess astrocytic physiology. The aim of the current study was to characterise the expression of NMDA receptors (NMDARs) in primary human astrocytes, and investigate their response to physiological and excitotoxic concentrations of the known endogenous NMDAR agonists, glutamate and quinolinic acid (QUIN). Primary cultures of human astrocytes were used to examine expression of these receptors at the mRNA level using RT-PCR and qPCR, and at the protein level using immunocytochemistry. The functionality role of the receptors was assessed using intracellular calcium influx experiments and measuring extracellular lactate dehydrogenase (LDH) activity in primary cultures of human astrocytes treated with glutamate and QUIN. We found that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B) are expressed in astrocytes, but at different levels. Calcium influx studies revealed that both glutamate and QUIN could activate astrocytic NMDARs, which stimulates Ca2+ influx into the cell and can result in dysfunction and death of astrocytes. Our data also show that the NMDAR ion channel blockers, MK801, and memantine can attenuate glutamate and QUIN mediated cell excitotoxicity. This suggests that the mechanism of glutamate and QUIN gliotoxicity is at least partially mediated by excessive stimulation of NMDARs. The present study is the first to provide definitive evidence for the existence of functional NMDAR expression in human primary astrocytes. This discovery has significant implications for redefining the cellular interaction between glia and neurons in both physiological processes and pathological conditions.Ming-Chak LeeKa Ka TingSeray AdamsBruce J BrewRoger ChungGilles J GuilleminPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e14123 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ming-Chak Lee Ka Ka Ting Seray Adams Bruce J Brew Roger Chung Gilles J Guillemin Characterisation of the expression of NMDA receptors in human astrocytes.
description	Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable of responding to endogenous neurotransmitters has resulted in the need to reassess astrocytic physiology. The aim of the current study was to characterise the expression of NMDA receptors (NMDARs) in primary human astrocytes, and investigate their response to physiological and excitotoxic concentrations of the known endogenous NMDAR agonists, glutamate and quinolinic acid (QUIN). Primary cultures of human astrocytes were used to examine expression of these receptors at the mRNA level using RT-PCR and qPCR, and at the protein level using immunocytochemistry. The functionality role of the receptors was assessed using intracellular calcium influx experiments and measuring extracellular lactate dehydrogenase (LDH) activity in primary cultures of human astrocytes treated with glutamate and QUIN. We found that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B) are expressed in astrocytes, but at different levels. Calcium influx studies revealed that both glutamate and QUIN could activate astrocytic NMDARs, which stimulates Ca2+ influx into the cell and can result in dysfunction and death of astrocytes. Our data also show that the NMDAR ion channel blockers, MK801, and memantine can attenuate glutamate and QUIN mediated cell excitotoxicity. This suggests that the mechanism of glutamate and QUIN gliotoxicity is at least partially mediated by excessive stimulation of NMDARs. The present study is the first to provide definitive evidence for the existence of functional NMDAR expression in human primary astrocytes. This discovery has significant implications for redefining the cellular interaction between glia and neurons in both physiological processes and pathological conditions.
format	article
author	Ming-Chak Lee Ka Ka Ting Seray Adams Bruce J Brew Roger Chung Gilles J Guillemin
author_facet	Ming-Chak Lee Ka Ka Ting Seray Adams Bruce J Brew Roger Chung Gilles J Guillemin
author_sort	Ming-Chak Lee
title	Characterisation of the expression of NMDA receptors in human astrocytes.
title_short	Characterisation of the expression of NMDA receptors in human astrocytes.
title_full	Characterisation of the expression of NMDA receptors in human astrocytes.
title_fullStr	Characterisation of the expression of NMDA receptors in human astrocytes.
title_full_unstemmed	Characterisation of the expression of NMDA receptors in human astrocytes.
title_sort	characterisation of the expression of nmda receptors in human astrocytes.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/6615200495244446b1a7e848f5274e08
work_keys_str_mv	AT mingchaklee characterisationoftheexpressionofnmdareceptorsinhumanastrocytes AT kakating characterisationoftheexpressionofnmdareceptorsinhumanastrocytes AT serayadams characterisationoftheexpressionofnmdareceptorsinhumanastrocytes AT brucejbrew characterisationoftheexpressionofnmdareceptorsinhumanastrocytes AT rogerchung characterisationoftheexpressionofnmdareceptorsinhumanastrocytes AT gillesjguillemin characterisationoftheexpressionofnmdareceptorsinhumanastrocytes
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Characterisation of the expression of NMDA receptors in human astrocytes.

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