Age modulates the nitric oxide system response in the ischemic cerebellum.
To determine whether age influences the nitric oxide system response to ischemia in the cerebellum, we have analyzed the levels of nitrogen oxides (NOx) and the expression of the different nitric oxide synthase isoforms (NOS) in mature adult (4-5 months old) and aged rats (24-27 months old) subjected to a transient global ischemia/reperfusion (I/R) model. We also analyzed the nitrated proteins and the glial fibrillary acidic protein (GFAP) expression. NOx concentration in adult rats, which more than doubled the values found in the aged rats, decreased after the ischemia and reperfusion. However, in the aged animals, these NOx levels did not significantly change after I/R. Constitutive isoforms were first down-regulated in the ischemic period, in both adult and aged animals. However, after 6 h of reperfusion, these isoforms were up-regulated, but only in aged rats. After I/R, iNOS was up-regulated in adults but down-regulated in the aged rats. Hence, after an episode of transient global ischemia and reperfusion, the aged cerebellum maintains a balanced NO production, silencing the iNOS isoform and inducing a weak expression of nNOS and eNOS; this allows NO physiological functions while avoiding possible undesirable effects such as the nitrative damage or astrocyte activation.
Blanco
Santos
S
Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071, Jaén, Spain.
Castro
Lourdes
L
Hernández
Raquel
R
Del Moral
María Luisa
ML
Pedrosa
Juan Angel
JA
Martínez-Lara
Esther
E
Siles
Eva
E
Peinado
María Angeles
MA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002526:Cerebellar Diseases / Q000378:metabolism* / Q000503:physiopathology; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III