Enhanced expression of brain interferon-alpha and serotonin transporter in immunologically induced fatigue in rats.
Immunologically induced fatigue was induced in rats by intraperitoneal injection of a synthetic double-stranded RNA, polyriboinosinic : polyribocytidylic acid (poly I:C). An injection of poly I:C (3 mg/kg) decreased the daily amounts of spontaneous running wheel activity to approximately 60% of the preinjection level until day 8. Quantitative analysis of mRNA levels demonstrated that interferon-alpha (IFN-alpha) and p38 mitogen-activated protein kinase mRNAs increased in the medial preoptic, paraventricular and ventromedial hypothalamic nuclei and in cortex on both days 1 and 8, while interleukin-1beta and an inhibitor of nuclear factor kappaB (IkappaB)-beta mRNAs increased on day 1, but recovered within a week. Serotonin transporter (5-HTT) mRNA also increased on days 1 and 8 after poly I:C injection in the same brain regions where IFN-alpha mRNA increased. The increased 5-HTT had a functional significance, because in vivo brain microdialysis revealed that an i.p. injection of poly I:C induced a decrease in the extracellular concentration of 5-HT in the prefrontal cortex; the decrease was blocked by local perfusion with a nonselective 5-HT reuptake inhibitor, imipramine. Finally, the poly I:C-induced fatigue was attenuated by a 5-HT1A receptor agonist but not by 5-HT2, 5-HT3 or dopamine D3 agonists. These findings, taken together, suggest that disorders in brain IFN-alpha and 5-HTT expression may be involved in the neuronal mechanisms of the poly I:C-induced fatigue.
Katafuchi
Toshihiko
T
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. kataf@physiol.med.kyushu-u.ac.jp
Kondo
Tetsuya
T
Take
Sachiko
S
Yoshimura
Megumu
M
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D018491:Dopamine Agonists / Q000494:pharmacology; D005221:Fatigue / Q000276:immunology* / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D018491:Dopamine Agonists; D020672:I-kappa B Proteins; D007369:Interferon Inducers; D016898:Interferon-alpha; D007375:Interleukin-1; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C