Brain cytokines and the 5-HT system during poly I:C-induced fatigue. 2006

Toshihiko Katafuchi, and Tetsuya Kondo, and Sachiko Take, and Megumu Yoshimura
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. kataf@physiol.med.kyushu-u.ac.jp

Fatigue is evoked not only by peripheral factors, such as muscle fatigue, but also by the central nervous system (CNS). For example, it is generally known that the feeling of fatigue is greatly influenced by psychological aspects, such as motivation. However, little is known about the central mechanisms of fatigue. The clinical symptoms of chronic fatigue syndrome (CFS) are shown to include disorders in neuroendocrine, autonomic, and immune systems. On the other hand, it has been demonstrated that cytokines produced in the brain play significant roles in neural-immune interactions through their various central actions, including hypothalamo-pituitary and sympathetic activation, as well as immunosuppression. In this article, using the immunologically induced fatigue model, which was achieved by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs, polyriboinosinic: polyribocytidylic acid (poly I:C) in rats, we show an involvement of brain interferon-alpha (IFN-alpha) and serotonin (5-HT) transporter (5-HTT) in the central mechanisms of fatigue. In the poly I:C-induced fatigue rats, expression of IFN-alpha and 5-HTT increased, while extracellular concentration of 5-HT in the medial prefrontal cortex decreased, probably on account of the enhanced expression of 5-HTT. Since the poly I:C-induced reduction of the running wheel activity was attenuated by a 5-HT(1A) receptor agonist, but not by 5-HT(2), 5-HT(3), or dopamine D(3) receptor agonists, it is suggested that the decrease in 5-HT actions on 5-HT(1A) receptors may at least partly contribute to the poly I:C-induced fatigue.

UI MeSH Term Description Entries
D007369 Interferon Inducers Agents that promote the production and release of interferons. They include mitogens, lipopolysaccharides, and the synthetic polymers Poly A-U and Poly I-C. Viruses, bacteria, and protozoa have been also known to induce interferons. Inducers, Interferon
D011070 Poly I-C Interferon inducer consisting of a synthetic, mismatched double-stranded RNA. The polymer is made of one strand each of polyinosinic acid and polycytidylic acid. Poly(I-C),Poly(rI).Poly(rC),Polyinosinic-Polycytidylic Acid,Polyinosinic-Polycytidylic Acid (High MW),Polyriboinosinic-Polyribocytidylic Acid,Polyribose Inosin-Cytidil,Inosin-Cytidil, Polyribose,Poly I C,Polyinosinic Polycytidylic Acid,Polyriboinosinic Polyribocytidylic Acid,Polyribose Inosin Cytidil
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D015213 Neuroimmunomodulation The biochemical and electrophysiological interactions between the NERVOUS SYSTEM and IMMUNE SYSTEM. Cholinergic Anti-inflammatory Pathway,Neuro-immune Axis,Neuro-immune Communication,Neuro-immune Interactions,Neuro-immunomodulation,Neuroimmune Axis,Neuroimmune Communication,Neuroimmune Interactions,Neuroimmune Processes,Vagal Anti-inflammatory Pathway,Vagal-immune Interactions,Neuroimmune Mechanisms,Neuroimmune Process,Anti-inflammatory Pathway, Cholinergic,Anti-inflammatory Pathway, Vagal,Cholinergic Anti inflammatory Pathway,Cholinergic Anti-inflammatory Pathways,Communication, Neuro-immune,Communication, Neuroimmune,Interaction, Neuro-immune,Interaction, Neuroimmune,Mechanism, Neuroimmune,Neuro immune Axis,Neuro immune Communication,Neuro immune Interactions,Neuro immunomodulation,Neuro-immune Communications,Neuro-immune Interaction,Neuroimmune Communications,Neuroimmune Interaction,Neuroimmune Mechanism,Process, Neuroimmune,Vagal Anti inflammatory Pathway,Vagal Anti-inflammatory Pathways,Vagal immune Interactions,Vagal-immune Interaction
D015673 Fatigue Syndrome, Chronic A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and FIBROMYALGIA. (From Semin Neurol 1998;18(2):237-42; Ann Intern Med 1994 Dec 15;121(12): 953-9) Chronic Fatigue Syndrome,Encephalomyelitis, Myalgic,Infectious Mononucleosis-Like Syndrome, Chronic,Postviral Fatigue Syndrome,Chronic Fatigue Disorder,Chronic Fatigue and Immune Dysfunction Syndrome,Chronic Fatigue-Fibromyalgia Syndrome,Myalgic Encephalomyelitis,Royal Free Disease,Systemic Exertion Intolerance Disease,Chronic Fatigue Disorders,Chronic Fatigue Fibromyalgia Syndrome,Chronic Fatigue Syndromes,Chronic Fatigue-Fibromyalgia Syndromes,Fatigue Disorder, Chronic,Fatigue Syndrome, Postviral,Fatigue Syndromes, Chronic,Fatigue-Fibromyalgia Syndrome, Chronic,Fatigue-Fibromyalgia Syndromes, Chronic,Infectious Mononucleosis Like Syndrome, Chronic,Postviral Fatigue Syndromes,Syndrome, Postviral Fatigue
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine

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