title: Effects of 3,3',5-triiodothyronine on microglial functions.
abstract: 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(+) /Ca(2+) exchanger (NCX), and small-conductance Ca(2+) -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.
authors: Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors: Yuki
authors: Y
authors: Mori
authors: Daichi
authors: D
authors: Tomonaga
authors: Anastasia
authors: A
authors: Kalashnikova
authors: Fumihiko
authors: F
authors: Furuya
authors: Nozomi
authors: N
authors: Akimoto
authors: Masataka
authors: M
authors: Ifuku
authors: Yuko
authors: Y
authors: Okuno
authors: Kaoru
authors: K
authors: Beppu
authors: Kyota
authors: K
authors: Fujita
authors: Toshihiko
authors: T
authors: Katafuchi
authors: Hiroki
authors: H
authors: Shimura
authors: Leonid P
authors: LP
authors: Churilov
authors: Mami
authors: M
authors: Noda
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D011339:Probenecid / Q000494:pharmacology; D011988:Receptors, Thyroid Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000277:Adjuvants, Pharmaceutic; D004791:Enzyme Inhibitors; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D000255:Adenosine Triphosphate; D011339:Probenecid; D013974:Thyroxine
keywords: GABA; microglia; migration; phagocytosis; thyroid hormone