Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties
Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preco...
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doaj-5506cf1b36bc423fb73e903f15dc40ce2020-11-25T03:43:21ZengSAGE PublishingASN Neuro1759-09141759-90912011-07-01310.1042/AN2010002910.1042_AN20100029Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective PropertiesEllora Sen0Anirban Basu1Lisa B Willing2Tracy F Uliasz3Jaimie L Myrkalo4Susan J Vannucci5Sandra J Hewett6Steven W Levison7 Department of Neurology and Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07103, U.S.A. National Brain Research Centre, Manesar 122 050, Haryana, India Department of Neural and Behavioral Science, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, U.S.A. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030, U.S.A. Department of Neurology and Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07103, U.S.A. Department of Pediatrics/Newborn Medicine, Weill Cornell Medical College, New York, NY 10065, U.S.A. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030, U.S.A. Department of Neurology and Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07103, U.S.A.Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O 2 ). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic proteinpositive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress.https://doi.org/10.1042/AN20100029 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ellora Sen Anirban Basu Lisa B Willing Tracy F Uliasz Jaimie L Myrkalo Susan J Vannucci Sandra J Hewett Steven W Levison |
spellingShingle |
Ellora Sen Anirban Basu Lisa B Willing Tracy F Uliasz Jaimie L Myrkalo Susan J Vannucci Sandra J Hewett Steven W Levison Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties ASN Neuro |
author_facet |
Ellora Sen Anirban Basu Lisa B Willing Tracy F Uliasz Jaimie L Myrkalo Susan J Vannucci Sandra J Hewett Steven W Levison |
author_sort |
Ellora Sen |
title |
Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties |
title_short |
Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties |
title_full |
Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties |
title_fullStr |
Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties |
title_full_unstemmed |
Pre-Conditioning Induces the Precocious Differentiation of Neonatal Astrocytes to Enhance Their Neuroprotective Properties |
title_sort |
pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties |
publisher |
SAGE Publishing |
series |
ASN Neuro |
issn |
1759-0914 1759-9091 |
publishDate |
2011-07-01 |
description |
Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O 2 ). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic proteinpositive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress. |
url |
https://doi.org/10.1042/AN20100029 |
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