Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18.
The present study investigated the possibility that acute stress might activate microglial cells. Wistar rats were exposed to 2 h period of restraint combined with water immersion stress prior to brain analysis by immunohistochemistry with OX-42, a marker of complement receptor CR3. A single session of stress provoked robust morphological microglial activation in the thalamus, hypothalamus, hippocampus, substantia nigra and central gray. These effects appeared as early as at 1 h of exposure and were further intensified at 2 h. Morphological activation was not accompanied with changes in markers of functional activation or of inflammation including interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS). Similar results were obtained with mice where the effects of stress were compared in animals null for interleukin-18 (IL-18 KO), a cytokine previously demonstrated to be modulated by stress and to contribute to microglia activation. The results demonstrated significant reduction of stress-induced microglial activation in IL-18 KO mice. The present study reports evidence that physical/emotional stress may induce morphological microglial activation in the brain and this activation is in part mediated by interleukin-18.
Sugama
S
S
Department of Physiology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan. sugama@nms.ac.jp
Fujita
M
M
Hashimoto
M
M
Conti
B
B
D000818:Animals; D001921:Brain / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D007031:Hypothalamus / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007101:Immersion; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000502:physiology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000473:pathology*; D013788:Thalamus / Q000473:pathology
D039481:CD11b Antigen; C509295:ITGAM protein, human; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II