炎症性疼痛モデルにおけるマクロファージ／ミクログリアの可視化
「はじめに」痛み研究における重要なトピックとして, 神経細胞と免疫細胞の相互作用が挙げられる. 神経損傷後や炎症後では, 末梢におけるマクロファージなどの浸潤・集積に加えて, 中枢におけるミクログリアの活性化が生じ, これらの免疫細胞は種々の炎症性メディエーターの産生を介して, 末梢神経と中枢神経を感作する. 特に, 脊髄後角ミクログリアの活性化は, 難治性の慢性疼痛である神経障害性疼痛などに関与することが明らかになっており, 重要な治療標的として注目されている. 近年, これらの細胞の可視化および人為的機能操作を可能にする技術開発が飛躍的に進み, その生理学的・病態学的役割がより明確になりつ...
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| Published in | PAIN RESEARCH Vol. 34; no. 1; pp. 31 - 38 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本疼痛学会
30.03.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0915-8588 2187-4697 |
| DOI | 10.11154/pain.34.31 |
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| Abstract | 「はじめに」痛み研究における重要なトピックとして, 神経細胞と免疫細胞の相互作用が挙げられる. 神経損傷後や炎症後では, 末梢におけるマクロファージなどの浸潤・集積に加えて, 中枢におけるミクログリアの活性化が生じ, これらの免疫細胞は種々の炎症性メディエーターの産生を介して, 末梢神経と中枢神経を感作する. 特に, 脊髄後角ミクログリアの活性化は, 難治性の慢性疼痛である神経障害性疼痛などに関与することが明らかになっており, 重要な治療標的として注目されている. 近年, これらの細胞の可視化および人為的機能操作を可能にする技術開発が飛躍的に進み, その生理学的・病態学的役割がより明確になりつつある. これらの点について, 本稿では, Iba-1 (iCre/+); CAG-floxed STOP tdTomatoレポーターマウスを組織透明化/三次元イメージング解析して得られた, 炎症性疼痛モデルの脊髄および脳におけるミクログリア活性化に関する著者らの知見を交えて概説したい. |
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| AbstractList | 「はじめに」痛み研究における重要なトピックとして, 神経細胞と免疫細胞の相互作用が挙げられる. 神経損傷後や炎症後では, 末梢におけるマクロファージなどの浸潤・集積に加えて, 中枢におけるミクログリアの活性化が生じ, これらの免疫細胞は種々の炎症性メディエーターの産生を介して, 末梢神経と中枢神経を感作する. 特に, 脊髄後角ミクログリアの活性化は, 難治性の慢性疼痛である神経障害性疼痛などに関与することが明らかになっており, 重要な治療標的として注目されている. 近年, これらの細胞の可視化および人為的機能操作を可能にする技術開発が飛躍的に進み, その生理学的・病態学的役割がより明確になりつつある. これらの点について, 本稿では, Iba-1 (iCre/+); CAG-floxed STOP tdTomatoレポーターマウスを組織透明化/三次元イメージング解析して得られた, 炎症性疼痛モデルの脊髄および脳におけるミクログリア活性化に関する著者らの知見を交えて概説したい. |
| Author | 内田, 仁司 阿部, 学 田井中, 一貴 崎村, 建司 |
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| DOI | 10.11154/pain.34.31 |
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Neurosci., 38 (2018) 9330-9337. 25) Sweitzer, S.M., Colburn, R.W., Rutkowski, M., DeLeo, J.A., Acute peripheral inflammation induces moderate glial activation and spinal IL1beta expression that correlates with pain behavior in the rat, Brain Res., 829 (1999) 209-221. 4) Grace, P.M., Strand, K.A., Galer, E.L., Urban, D.J., Wang, X., Baratta, M.V., Fabisiak, T.J., Anderson, N.D., Cheng, K., Greene, L.I., Berkelhammer, D., Zhang, Y., Ellis, A.L., Yin, H.H., Campeau, S.,Rice, K.C., Roth, B.L., Maier, S.F., Watkins, L.R., Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3inflammasome activation, Proc. Natl. Acad. Sci. USA,113 (2016) E3441-3450. 8) Hernstadt, H., Wang, S., Lim, G., Mao, J., Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis, Brain Res., 1286 (2009) 42-52. 13) Kohno, K., Kitano, J., Kohro, Y., Tozaki-Saitoh, H., Inoue, K., Tsuda, M., Temporal Kinetics of Microgliosis in the Spinal Dorsal Horn after Peripheral Nerve Injury in Rodents, Biol. Pharm. Bull., 41 (2018) 1096-1102. 18) Nakayama, H., Abe, M., Morimoto, C., Iida, T., Okabe, S., Sakimura, K., Hashimoto, K., Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum, Nat. Commun., 9 (2018) 2830. 19) Prinz, M., Erny, D., Hagemeyer, N., Ontogeny and homeostasis of CNS myeloid cells, Nat. Immunol., 18 (2017) 385-392. |
| References_xml | – reference: 14) Konishi, H., Kobayashi, M., Kunisawa, T., Imai, K., Sayo, A., Malissen, B., Crocker, P.R., Sato, K.,Kiyama, H., Siglec-H is a microglia-specific marker that discriminates microglia from CNS associated macrophages and CNS-infiltrating monocytes, Glia, 65 (2017) 1927-1943. – reference: 5) Grace, P.M., Wang, X., Strand, K.A., Baratta, M.V., Zhang, Y., Galer, E.L., Yin, H., Maier, S.F., Watkins, L.R., DREADDed microglia in pain:Implications for spinal inflammatory signaling in male rats, Exp. Neurol., 304 (2018) 125-131. – reference: 16) Lin, T., Li, K., Zhang, F.Y., Zhang, Z.K., Light, A.R., Fu, K.Y., Dissociation of spinal microglia morpho logical activation and peripheral inflammation in inflammatory pain models, J. Neuroimmunol, 192(2007) 40-48. – reference: 21) Richardson, D.S., Lichtman, J.W., Clarifying Tissue Clearing, Cell, 162 (2015) 246-257. – reference: 23) Salter, M.W., Stevens, B., Microglia emerge as central players in brain disease, Nat. Med., 23 (2017) 1018-1027. – reference: 6) Gu, N., Peng, J., Murugan, M., Wang, X., Eyo, U.B., Sun, D., Ren, Y., DiCicco-Bloom, E., Young, W., Dong, H., Wu, L.J., Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury, Cell Rep., 16 (2016) 605-614. – reference: 10) Huber, J.D., Campos, C.R., Mark, K.S., Davis, T.P., Alterations in blood-brain barrier ICAM 1 expression and brain microglial activation after lambda-carrageenan-induced inflammatory pain, Am. J. Physiol. Heart Circ. Physiol., 290 (2006) H732-740. – reference: 9) Hua, X.Y., Svensson, C.I., Matsui, T., Fitzsimmons, B., Yaksh, T.L., Webb, M., Intrathecal minocycline attenuates peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in spinal microglia, Eur. J. Neurosci., 22 (2005) 2431-2440. – reference: 15) Li, Q., Barres, B.A., Microglia and macrophages in brain homeostasis and disease, Nat. Rev. Immunol., 18 (2018) 225-242. – reference: 19) Prinz, M., Erny, D., Hagemeyer, N., Ontogeny and homeostasis of CNS myeloid cells, Nat. Immunol., 18 (2017) 385-392. – reference: 7) Hama, H., Kurokawa, H., Kawano, H., Ando, R., Shimogori, T., Noda, H., Fukami, K., Sakaue Sawano, A., Miyawaki, A., Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain, Nat. Neurosci., 14 (2011) 1481-1488. – reference: 25) Sweitzer, S.M., Colburn, R.W., Rutkowski, M., DeLeo, J.A., Acute peripheral inflammation induces moderate glial activation and spinal IL1beta expression that correlates with pain behavior in the rat, Brain Res., 829 (1999) 209-221. – reference: 1) Clark, A.K., Gentry, C., Bradbury, E.J., McMahon, S.B., Malcangio, M., Role of spinal microglia in rat models of peripheral nerve injury and inflammation, Eur. J. Pain, 11 (2007) 223-230. – reference: 22) Roberts, J., Ossipov, M.H., Porreca, F., Glial activation in the rostroventromedial medulla pro motes descending facilitation to mediate inflammatory hypersensitivity, Eur. J. Neurosci., 30 (2009) 229-241. – reference: 2) Dodt, H.U., Leischner, U., Schierloh, A., Jahrling, N., Mauch, C.P., Deininger, K., Deussing, J.M., Eder, M., Zieglgansberger, W., Becker, K., Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain, Nat. Methods, 4 (2007) 331-336. – reference: 28) Tashima, R., Mikuriya, S., Tomiyama, D., Shiratori-Hayashi, M., Yamashita, T., Kohro, Y., Tozaki-Saitoh, H., Inoue, K., Tsuda, M., Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury, Sci. Rep., 6 (2016) 23701. – reference: 29) Zhao, P., Waxman, S.G., Hains, B.C., Modulation of thalamic nociceptive processing after spinal cord injury through remote activation of thalamic microglia by cysteine cysteine chemokine ligand 21, J. Neurosci., 27 (2007) 8893-8902. – reference: 27) Tainaka, K., Murakami, T.C., Susaki, E.A., Shimizu, C., Saito, R., Takahashi, K., Hayashi Takagi, A., Sekiya, H., Arima, Y., Nojima, S., Ikemura, M., Ushiku, T., Shimizu, Y., Murakami,M., Tanaka, K.F., Iino, M., Kasai, H., Sasaoka, T.,Kobayashi, K., Miyazono, K., Morii, E., Isa, T.,Fukayama, M., Kakita, A., Ueda, H.R., Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents, Cell Rep., 24 (2018) 2196-2210 e2199. – reference: 13) Kohno, K., Kitano, J., Kohro, Y., Tozaki-Saitoh, H., Inoue, K., Tsuda, M., Temporal Kinetics of Microgliosis in the Spinal Dorsal Horn after Peripheral Nerve Injury in Rodents, Biol. Pharm. Bull., 41 (2018) 1096-1102. – reference: 11) Inoue, K., Tsuda, M., Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential, Nat. Rev. Neurosci., 19 (2018) 138-152. – reference: 24) Susaki, E.A., Tainaka, K., Perrin, D., Kishino, F., Tawara, T., Watanabe, T.M., Yokoyama, C., Onoe, H., Eguchi, M., Yamaguchi, S., Abe, T., Kiyonari, H., Shimizu, Y., Miyawaki, A., Yokota, H., Ueda, H.R., Whole-brain imaging with singl e-cell resolution using chemical cocktails and computational analysis, Cell, 157 (2014) 726-739. – reference: 3) Ertürk, A., Mauch, C.P., Hellal, F., Forstner, F., Keck, T., Becker, K., Jahrling, N., Steffens, H., Richter, M., Hubener, M., Kramer, E., Kirchhoff, F., Dodt, H.U., Bradke, F., Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury, Nat. Med., 18 (2012) 166-171. – reference: 8) Hernstadt, H., Wang, S., Lim, G., Mao, J., Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis, Brain Res., 1286 (2009) 42-52. – reference: 26) Tainaka, K., Kubota, S.I., Suyama, T.Q., Susaki, E.A., Perrin, D., Ukai-Tadenuma, M., Ukai, H., Ueda, H.R., Whole-body imaging with singlecell resolution by tissue decolorization, Cell, 159 (2014) 911-924. – reference: 18) Nakayama, H., Abe, M., Morimoto, C., Iida, T., Okabe, S., Sakimura, K., Hashimoto, K., Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum, Nat. Commun., 9 (2018) 2830. – reference: 20) Raghavendra, V., Tanga, F.Y., DeLeo, J.A., Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS, Eur. J. Neurosci., 20 (2004) 467-473. – reference: 12) Ke, MT, Fujimoto, S, Imai, T., SeeDB: a simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction, Nat. Neurosci., 16 (2013) 1154-1161. – reference: 4) Grace, P.M., Strand, K.A., Galer, E.L., Urban, D.J., Wang, X., Baratta, M.V., Fabisiak, T.J., Anderson, N.D., Cheng, K., Greene, L.I., Berkelhammer, D., Zhang, Y., Ellis, A.L., Yin, H.H., Campeau, S.,Rice, K.C., Roth, B.L., Maier, S.F., Watkins, L.R., Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3inflammasome activation, Proc. Natl. Acad. Sci. USA,113 (2016) E3441-3450. – reference: 17) Mano, T., Albanese, A., Dodt, H.U., Erturk, A., Gradinaru, V., Treweek, J.B., Miyawaki, A., Chung, K., Ueda, H.R., Whole-Brain Analysis of Cells and Circuits by Tissue Clearing and Light-Sheet Microscopy, J. Neurosci., 38 (2018) 9330-9337. |
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| Title | 炎症性疼痛モデルにおけるマクロファージ／ミクログリアの可視化 |
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