Effects of 3,3 ', 5-Triiodothyronine on Microglial Functions. / Mori, Yuki; Tomonaga, Daichi; Kalashnikova, Anastasia; Furuya, Fumihiko; Akimoto, Nozomi; Ifuku, Masataka; Okuno, Yuko; Beppu, Kaoru; Fujita, Kyota; Katafuchi, Toshihiko; Shimura, Hiroki; Churilov, Leonid P.; Noda, Mami.
In: GLIA, Vol. 63, No. 5, 05.2015, p. 906-920.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Effects of 3,3 ', 5-Triiodothyronine on Microglial Functions
AU - Mori, Yuki
AU - Tomonaga, Daichi
AU - Kalashnikova, Anastasia
AU - Furuya, Fumihiko
AU - Akimoto, Nozomi
AU - Ifuku, Masataka
AU - Okuno, Yuko
AU - Beppu, Kaoru
AU - Fujita, Kyota
AU - Katafuchi, Toshihiko
AU - Shimura, Hiroki
AU - Churilov, Leonid P.
AU - Noda, Mami
PY - 2015/5
Y1 - 2015/5
N2 - 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 TR-knock-out (KO) suppressed T3-induced microglial migration and morphological change. The T3-induced microglial migration or membrane ruffling was attenuated by inhibiting G(i/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 GABA(A) and GABA(B) 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. GLIA 2015:63:906-920
AB - 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 TR-knock-out (KO) suppressed T3-induced microglial migration and morphological change. The T3-induced microglial migration or membrane ruffling was attenuated by inhibiting G(i/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 GABA(A) and GABA(B) 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. GLIA 2015:63:906-920
KW - thyroid hormone
KW - microglia
KW - migration
KW - phagocytosis
KW - GABA
KW - BLOOD-BRAIN-BARRIER
KW - HORMONE RECEPTOR-ALPHA
KW - ANION-TRANSPORTING POLYPEPTIDES
KW - THYROID-HORMONE
KW - NA+/CA2+ EXCHANGER
KW - CELL-MIGRATION
KW - CEREBELLAR ASTROCYTES
KW - ALZHEIMERS-DISEASE
KW - CULTURED MICROGLIA
KW - IN-VIVO
U2 - 10.1002/glia.22792
DO - 10.1002/glia.22792
M3 - статья
VL - 63
SP - 906
EP - 920
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 5
ER -
ID: 5769650