Microglial activation in immunologically induced fatigue

Masataka Ifuku, Shamim Hossain, Toshihiko Katafuchi

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1 Citation (Scopus)


The clinical symptoms of chronic fatigue syndrome (CFS) have been shown to include disorders in the 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, such as activation of the hypothalamo-pituitary axis. We have recently developed an animal for fatigue induced by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs, polyriboinosinic: polyribocytidylic acid (poly I:C, 3 mg/kg), in rats, and shown a decrease in the daily amounts of spontaneous running wheel activity to about 60% of preinjection level for more than 1 week. Simultaneously, mRNA for Interleukin-1β (IL-1β) increased for 1 day following poly I:C injection in the same hypothalamic nuclei. It is thus possible that brain cytokines may play some roles in the central mechanisms of fatigue. In this review article, we showed a role of microglia, one of the major cytokine-producing cells in the central nervous system, in the onset of fatigue using immunologically induced fatigue model rats. Microglia were morphologically activated in the medial preoptic area (MPO) and periventricular hypothalamic nucleus (Pe) 24-48 hrs after the injection of poly I:C. Pretreatment with minocycline for the consecutive 3 days (40 mg/kg/day), the poly I:C-induced decrease in the running wheel activity recovered to the base line levels, and the activation of microglia was suppressed. Following poly I:C injection, the expression of IL-1β was markedly increased in microglia in the MPO and Pe, since the IL-1β-positive cells were double-labeled with an antibody for the microglia marker, Iba-1. Furthermore, the poly I:C-induced increase in the expression of IL-1β was also prevented by pretreatment with minocycline. These findings, taken together, suggest that the activation of microglia, which is accompanied by the enhanced expression of IL-1β, is involved in the onset of the immunologically induced fatigue.

Original languageEnglish
Pages (from-to)245-253
Number of pages9
JournalAdvances in Neuroimmune Biology
Issue number4
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrinology
  • Endocrine and Autonomic Systems


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