Basal and IL-1beta-stimulated cytokine and neuropeptide mRNA expression in brain regions of young and old Long-Evans rats.
Young and old Long-Evans rats respond with fevers of equal magnitude and duration to the brain administration of interleukin-1beta (IL-1beta). Here, we characterized brain regional mRNA expression of cytokine and neuropeptide components in response to the brain administration of IL-1beta. We used specific and highly sensitive RNase protection assays to determine mRNA changes for IL-1beta, IL-1 receptor type I (IL-1RI), IL-1R accessory proteins I and II (IL-1R AcP I and II), IL-1 receptor antagonist (IL-1Ra), transforming growth factor-beta1 (TGF-beta1), glycoprotein 130 (gp 130), leptin receptor (OB-R), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the cerebellum, parieto-frontal cortex, hippocampus, hypothalamus, and midbrain of male young (3-5 months) and old (24-26 months) Long-Evans rats. In both young and old rats, IL-1beta induced a significant up-regulation of cerebellar IL-1Ra, IL-1RI, and TGF-beta1 mRNAs; hippocampal TGF-beta1 mRNA; hypothalamic IL-1beta, IL-1Ra, TGF-beta1, and gp 130 mRNAs; and midbrain IL-1beta and TGF-beta1 mRNAs. There were no age-related differences in any cytokine mRNA levels under basal or IL-1beta-stimulated conditions. Levels of hypothalamic POMC mRNA were different between age groups under basal and stimulated conditions. IL-1R AcP I and leptin receptor did not change in any brain region from either young or old rats, suggesting specificity of transcriptional changes. The data show that old Long-Evans rats are not defective in their capacity to develop an appropriate cytokine response to the brain administration of IL-1beta. The implications of these findings for neuroimmunological-neuroinflammatory and neurotoxic/neurodegenerative processes are discussed.
Gayle
D
D
Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark, DE 19716-2590, USA.
Ilyin
S E
SE
Romanovitch
A E
AE
Peloso
E
E
Satinoff
E
E
Plata-Salamán
C R
CR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005334:Fever / Q000139:chemically induced; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D011333:Pro-Opiomelanocortin