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AMPA receptor downregulation induced by ischaemia/reperfusion is attenuated by age and blocked by meloxicam
Author(s) -
Montori S.,
Dos_Anjos S.,
RíosGranja M. A.,
PérezGarcía C. C.,
FernándezLópez A.,
MartínezVillayandre B.
Publication year - 2010
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2010.01086.x
Subject(s) - meloxicam , downregulation and upregulation , ampa receptor , medicine , ischemia , anesthesia , receptor , pharmacology , cardiology , glutamate receptor , chemistry , biochemistry , gene
S. Montori, S. Dos_Anjos, M. A. Ríos‐Granja, C. C. Pérez‐García, A. Fernández‐López and B. Martínez‐Villayandre (2010) Neuropathology and Applied Neurobiology 36, 436–447
AMPA receptor downregulation induced by ischaemia/reperfusion is attenuated by age and blocked by meloxicamAim: Stroke prevalence increases with age, while alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid receptor (AMPAR) and inflammation have been related to ischaemia‐induced damage. This study shows how age and treatment with an anti‐inflammatory agent (meloxicam) modify the levels of AMPAR subunits GluR1 and GluR2, as well as the mRNA levels of the GluR2‐editing enzyme, ADAR2, in a global brain ischaemia/reperfusion (I/R) model. Methods: Two days after global ischaemia CA1, CA3, dentate gyrus and cerebral cortex were obtained from sham‐operated and I/R‐injured 3‐ and 18‐month‐old Sprague–Dawley rats. Real time polymerase chain reaction, Western blotting and immunohistochemical assays were performed. Meloxicam treatment was assayed on young animals. Results: Data showed that age attenuates the downregulation induced by I/R in the AMPAR subunits GluR1 and GluR2 and modifies the GluR1/GluR2 mRNA level ratio in a structure‐dependent way. The study of the ADAR2 mRNA levels showed more downregulation in older animals than young ones. Meloxicam treatment prevented the transcriptional arrest induced by I/R. Conclusion: Our data suggest that changes in the AMPAR isoforms could be associated with ageing in the different structures studied. Although GluR2 editing seems to be involved in age‐dependent vulnerability to ischaemia supporting the ‘GluR2 hypothesis’, this alone does not explain the differential vulnerability in the different brain regions. Finally, inflammation could play a role in protection from I/R‐induced injury.