Effects of 3,3',5-triiodothyronine on microglial functions

Yuki Mori, Daichi Tomonaga, Anastasia Kalashnikova, Fumihiko Furuya, Nozomi Akimoto, Masataka Ifuku, Yuko Okuno, Kaoru Beppu, Kyota Fujita, Toshihiko Katafuchi, Hiroki Shimura, Leonid P. Churilov, Mami Noda

研究成果: Contribution to journalArticle

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L-tri-iodothyronine (3, 3', 5-triiodothyronine, T3) is an active form of the thyroid hormone (TH) essential for the development and function of the CNS. Though nongenomic effect of TH, its plasma membrane-bound receptor, and its signaling has been identified, precise function in each cell type of the CNS remained to be investigated. Clearance of cell debris and apoptotic cells by microglia phagocytosis is a critical step for the restoration of damaged neuron-glia networks. Here we report nongenomic effects of T3 on microglial functions. Exposure to T3 increased migration, membrane ruffling and phagocytosis of primary cultured mouse microglia. Injection of T3 together with stab wound attracted more microglia to the lesion site in vivo. Blocking TH transporters and receptors (TRs) or TRα-knock-out (KO) suppressed T3-induced microglial migration and morphological change. The T3-induced microglial migration or membrane ruffling was attenuated by inhibiting Gi/o-protein as well as NO synthase, and subsequent signaling such as phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). Inhibitors for Na+/K+-ATPase, reverse mode of Na+/Ca2+ exchanger (NCX), and small-conductance Ca2+-dependent K+ (SK) channel also attenuated microglial migration or phagocytosis. Interestingly, T3-induced microglial migration, but not phagocytosis, was dependent on GABAA and GABAB receptors, though GABA itself did not affect migratory aptitude. Our results demonstrate that T3 modulates multiple functional responses of microglia via multiple complex mechanisms, which may contribute to physiological and/or pathophysiological functions of the CNS.

元の言語英語
ページ(範囲)906-920
ページ数15
ジャーナルGLIA
63
発行部数5
DOI
出版物ステータス出版済み - 5 1 2015

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

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    Mori, Y., Tomonaga, D., Kalashnikova, A., Furuya, F., Akimoto, N., Ifuku, M., Okuno, Y., Beppu, K., Fujita, K., Katafuchi, T., Shimura, H., Churilov, L. P., & Noda, M. (2015). Effects of 3,3',5-triiodothyronine on microglial functions. GLIA, 63(5), 906-920. https://doi.org/10.1002/glia.22792