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A depletable pool of adenosine in area CA1 of the rat hippocampus

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Pearson, Tim, Nuritova, Feruza, Caldwell, Darren, Dale, Nicholas and Frenguelli, Bruno G.. (2001) A depletable pool of adenosine in area CA1 of the rat hippocampus. Journal of Neuroscience, Vol.21 (No.7). pp. 2298-2307. ISSN 0270-6474

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Abstract

Adenosine plays a major modulatory and neuroprotective role in the mammalian CNS. During cerebral metabolic stress, such as hypoxia or ischemia, the increase in extracellular adenosine inhibits excitatory synaptic transmission onto vulnerable neurons via presynaptic adenosine A1 receptors, thereby reducing the activation of postsynaptic glutamate receptors. Using a combination of extracellular and whole-cell recordings in the CA1 region of hippocampal slices from 12- to 24-d-old rats, we have found that this protective depression of synaptic transmission weakens with repeated exposure to hypoxia, thereby allowing potentially damaging excitation to both persist for longer during oxygen deprivation and recover more rapidly on reoxygenation. This phenomenon is unlikely to involve A1 receptor desensitization or impaired nucleoside transport. Instead, by using the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine and a novel adenosine sensor, we demonstrate that adenosine production is reduced with repeated episodes of hypoxia. Furthermore, this adenosine depletion can be reversed at least partially either by the application of exogenous adenosine, but not by a stable A1 agonist, N6-cyclopentyladenosine, or by endogenous means by prolonged (2 hr) recovery between hypoxic episodes. Given the vital neuroprotective role of adenosine, these findings suggest that depletion of adenosine may underlie the increased neuronal vulnerability to repetitive or secondary hypoxia/ischemia in cerebrovascular disease and head injury.

Item Type:	Journal Article
Subjects:	Q Science > QL Zoology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Adenosine deaminase, Cerebral anoxia, Hippocampus (Brain), Head -- Wounds and injuries, Rats -- Physiology
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Date:	1 April 2001
Volume:	Vol.21
Number:	No.7
Page Range:	pp. 2298-2307
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Royal Society (Great Britain), Wellcome Trust (London, England), Scottish Hospital Endowments Research Trust (SHERT), Tenovus - The Cancer Charity, Anonymous Trust (Dundee, Scotland), Caledonian Research Foundation (CRF)
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URI:	http://wrap.warwick.ac.uk/id/eprint/3005