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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Bibliographic Details
Published in:	ASN neuro Vol. 3; no. 3; p. e00062
Main Authors:	Sen, Ellora, Basu, Anirban, Willing, Lisa B, Uliasz, Tracy F, Myrkalo, Jaimie L, Vannucci, Susan J, Hewett, Sandra J, Levison, Steven W
Format:	Journal Article
Language:	English
Published:	United States American Society for Neurochemistry 26-07-2011 Taylor & Francis
Subjects:	Animals Animals, Newborn Astrocytes - cytology Astrocytes - physiology Cell Differentiation - physiology Cells, Cultured Excitatory Amino Acid Transporter 1 - metabolism Glial Fibrillary Acidic Protein - metabolism Glutamate-Ammonia Ligase - metabolism Glutamic Acid - metabolism Hypoxia - metabolism Ischemic Preconditioning Neurons - cytology Neurons - physiology Neuroprotective Agents Rats Rats, Wistar
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Summary:	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% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1759-0914 1759-0914
DOI:	10.1042/AN20100029