Document Detail


Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1.
MedLine Citation:
PMID:  23035103     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
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:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13945-55     Citation Subset:  IM    
Affiliation:
Division of Nutritional Sciences, Program in Integrative Immunology and Behavior, University of Illinois, Urbana Illinois 61801, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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
Comments/Corrections

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