| Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1. | |
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MedLine Citation:
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PMID: 23035103 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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After hypoxia, a critical adverse outcome is the inability to create new memories. How anterograde amnesia develops or resolves remains elusive, but a link to brain-based IL-1 is suggested due to the vital role of IL-1 in both learning and brain injury. We examined memory formation in mice exposed to acute hypoxia. After reoxygenation, memory recall recovered faster than memory formation, impacting novel object recognition and cued fear conditioning but not spatially cued Y-maze performance. The ability of mice to form new memories after hypoxia/reoxygenation was accelerated in IL-1 receptor 1 knockout (IL-1R1 KO) mice, in mice receiving IL-1 receptor antagonist (IL-1RA), and in mice given the caspase 1 inhibitor Ac-YVAD-CMK. Mechanistically, hypoxia/reoxygenation more than doubled caspase 1 activity in the brain, which was localized to the amygdala compared to the hippocampus. This reoxygenation-dependent activation of caspase 1 was prevented by broad-spectrum adenosine receptor (AR) antagonism with caffeine and by targeted A1/A2A AR antagonism with 8-cyclopentyl-1,3-dipropylxanthine plus 3,7-dimethyl-1-propargylxanthine. Additionally, perfusion of adenosine activated caspase 1 in the brain, while caffeine blocked this action by adenosine. Finally, resolution of anterograde amnesia was improved by both caffeine and by targeted A1/A2A AR antagonism. These findings indicate that amygdala-based anterograde amnesia after hypoxia/reoxygenation is sustained by IL-1β generated through adenosine-dependent activation of caspase 1 after reoxygenation. |
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Authors:
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Gabriel S Chiu; Diptaman Chatterjee; Patrick T Darmody; John P Walsh; Daryl D Meling; Rodney W Johnson; Gregory G Freund |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 32 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-04 Completed Date: 2013-01-17 Revised Date: 2013-04-05 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 13945-55 Citation Subset: IM |
Affiliation:
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Division of Nutritional Sciences, Program in Integrative Immunology and Behavior, University of Illinois, Urbana Illinois 61801, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
/
pharmacology,
physiology* Amino Acid Chloromethyl Ketones / pharmacology Amnesia, Anterograde / enzymology*, etiology, physiopathology Amygdala / drug effects, enzymology, physiology* Animals Caffeine / pharmacology Caspase 1 / drug effects, physiology* Caspase Inhibitors / pharmacology Conditioning, Classical / drug effects, physiology Cues Enzyme Activation Fear / drug effects, physiology Hypoxia, Brain / complications*, physiopathology Interleukin 1 Receptor Antagonist Protein / pharmacology MAP Kinase Signaling System Male Maze Learning / drug effects, physiology Mental Recall Mice Mice, Inbred C57BL Mice, Knockout Oxygen / metabolism, pharmacology Receptors, Interleukin-1 Type I / deficiency Receptors, Purinergic P1 / physiology Recognition (Psychology) / drug effects, physiology Theobromine / analogs & derivatives, pharmacology Xanthines / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AA019357/AA/NIAAA NIH HHS; DK064862/DK/NIDDK NIH HHS; DK59802/DK/NIDDK NIH HHS; NS058525/NS/NINDS NIH HHS; R01 DK064862/DK/NIDDK NIH HHS; R01 NS058525/NS/NINDS NIH HHS; RC1 AA019357/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Caspase Inhibitors; 0/Interleukin 1 Receptor Antagonist Protein; 0/N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; 0/Receptors, Interleukin-1 Type I; 0/Receptors, Purinergic P1; 0/Xanthines; 102146-07-6/1,3-dipropyl-8-cyclopentylxanthine; 58-08-2/Caffeine; 58-61-7/Adenosine; 5YFR5SPS6T/3,7-dimethyl-1-propargylxanthine; 7782-44-7/Oxygen; 83-67-0/Theobromine; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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