九州大学 研究者情報
論文一覧
津田 誠(つだ まこと) データ更新日:2019.06.06

教授 /  薬学研究院 臨床薬学部門 ライフイノベーション分野


原著論文
1. 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, 10.1248/bpb.b18-00278, 2018.05.
2. Hidetoshi Saitoh, Junya Masuda, Ryu Kawada, Chinami Kojima, Sosuke Yoneda, Takahiro Masuda, Kazuhide Inoue, Tsuda Makoto, Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development, GLIA, 10.1002/glia.23570, 67, 4, 729-740, 2019.04, [URL], Microglia, which are pathological effectors and amplifiers in the central nervous system, undergo various forms of activation. A well-studied microglial-induced pathological paradigm, spinal microglial activation following peripheral nerve injury (PNI), is a key event for the development of neuropathic pain but the transcription factors contributing to microglial activation are less understood. Herein, we demonstrate that MafB, a dominant transcriptional regulator of mature microglia, is involved in the pathology of a mouse model of neuropathic pain. PNI caused a rapid and marked increase of MafB expression selectively in spinal microglia but not in neurons. We also found that the microRNA mir-152 in the spinal cord which targets MafB expression decreased after PNI, and intrathecal administration of mir-152 mimic suppressed the development of neuropathic pain. Reduced MafB expression using heterozygous Mafb deficient mice and by intrathecal administration of siRNA alleviated the development of PNI-induced mechanical hypersensitivity. Furthermore, we found that intrathecal transfer of Mafb deficient microglia did not induce mechanical hypersensitivity and that conditional Mafb knockout mice did not develop neuropathic pain after PNI. We propose that MafB is a key mediator of the PNI-induced phenotypic alteration of spinal microglia and neuropathic pain development..
3. Shiratori-Hayashi M, Hasegawa A, Toyonaga H, Andoh T, Nakahara T, Kido-Nakahara M, Furue M, Kuraishi Y, Inoue K, Dong X, Tsuda M, Role of P2X3 receptors in scratching behavior in mouse models, J Allergy Clin Immunol, 10.1016/j.jaci.2018.10.053, 143, 3, 1252-1254.e8, 2019.03.
4. Masaya Yasui, Yuki Menjyo, Kyohei Tokizane, Akiko Shiozawa, Tsuda Makoto, Kazuhide Inoue, Hiroshi Kiyama, Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome, Journal of Neuroinflammation, 10.1186/s12974-019-1456-x, 16, 1, 2019.03, [URL], Background: Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior without peripheral tissue damage and/or inflammation. The present study addressed the mechanism underlying the association between pain and chronic stress using this rat model. Methods: Chronic or continuous stress-loading (CS) model rats, housed in a cage with a thin level of water (1.5 cm in depth), were used. The von Frey test and pressure pain test were employed to measure pain behavior. The neuronal and microglial activations were immunohistochemically demonstrated with antibodies against ATF3 and Iba1. Electromyography was used to evaluate muscle activity. Results: The expression of ATF3, a marker of neuronal hyperactivity or injury, was first observed in the lumbar dorsal root ganglion (DRG) neurons 2 days after CS initiation. More than 50% of ATF3-positive neurons simultaneously expressed the proprioceptor markers TrkC or VGluT1, whereas the co-expression rates for TrkA, TrkB, IB4, and CGRP were lower than 20%. Retrograde labeling using fluorogold showed that ATF3-positive proprioceptive DRG neurons mainly projected to the soleus. Substantial microglial accumulation was observed in the medial part of the dorsal horn on the fifth CS day. Microglial accumulation was observed around a subset of motor neurons in the dorsal part of the ventral horn on the sixth CS day. The motor neurons surrounded by microglia were ATF3-positive and mainly projected to the soleus. Electromyographic activity in the soleus was two to three times higher in the CS group than in the control group. These results suggest that chronic proprioceptor activation induces the sequential activation of neurons along the spinal reflex arc, and the neuronal activation further activates microglia along the arc. Proprioceptor suppression by ankle joint immobilization significantly suppressed the accumulation of microglia in the spinal cord, as well as the pain behavior. Conclusion: Our results indicate that proprioceptor-induced microglial activation may be a key player in the initiation and maintenance of abnormal pain in patients with CFS..
5. Tatsuhiro Igawa, Shuhei Kishikawa, Yoshito Abe, Tomohiro Yamashita, Saki Nagai, Mitsunori Shiroishi, Chinatsu Shinozaki, Hiroyuki Tanaka, Hidetoshi Saitoh, Tsuda Makoto, Kazuhide Inoue, Tadashi Ueda, Evidence for detection of rat P2X4 receptor expressed on cells by generating monoclonal antibodies recognizing the native structure, Purinergic Signalling, 10.1007/s11302-019-09646-5, 2019.01, [URL], P2X purinergic receptors are ATP-driven ionic channels expressed as trimers and showing various functions. A subtype, the P2X4 receptor present on microglial cells is highly involved in neuropathic pain. In this study, in order to prepare antibodies recognizing the native structure of rat P2X4 (rP2X4) receptor, we immunized mice with rP2X4’s head domain (rHD, Gln111–Val167), which possesses an intact structure stabilized by S-S bond formation (Igawa and Abe et al. FEBS Lett. 2015), as an antigen. We generated five monoclonal antibodies with the ability to recognize the native structure of its head domain, stabilized by S-S bond formation. Site-directed mutagenesis revealed that Asn127 and Asp131 of the rHD, in which combination of these amino acid residues is only conserved in P2X4 receptor among P2X family, were closely involved in the interaction between rHD and these antibodies. We also demonstrated the antibodies obtained here could detect rP2X4 receptor expressed in 1321N1 human astrocytoma cells..
6. Shota Yamamoto, Nobuaki Egashira, Tsuda Makoto, Satohiro Masuda, Riluzole prevents oxaliplatin-induced cold allodynia via inhibition of overexpression of transient receptor potential melastatin 8 in rats, Journal of Pharmacological Sciences, 10.1016/j.jphs.2018.10.006, 138, 3, 214-217, 2018.11, [URL], Oxaliplatin causes acute cold hypersensitivity in most patients. We previously reported oxalate derived from oxaliplatin induced cold allodynia via overexpression of transient receptor potential melastatin 8 (TRPM8) in the dorsal root ganglion (DRG) in rats. In this study, we examined the effect of riluzole on oxaliplatin-induced cold allodynia. In cultured DRG neurons, riluzole suppressed oxalate-induced increase of the number of menthol (TRPM8 agonist)-sensitive cells. Moreover, riluzole prevented cold allodynia and increase in levels of TRPM8 mRNA in oxaliplatin-treated rats. These results suggest that riluzole prevents oxaliplatin-induced cold allodynia via inhibition of TRPM8 overexpression in the DRG..
7. Sasaguri T, Taguchi T, Murata Y, Kobayashi K, Iizasa S, Iizasa E, Tsuda M, Hirakawa N, Hara H, Yoshida H, Yasaka T Interleukin-27 controls basal pain threshold in physiological and pathological conditions., Interleukin-27 controls basal pain threshold in physiological and pathological conditions, Sci Rep, 10.1038/s41598-018-29398-3, 8, 1, 11022, 2018.06.
8. Tao Chen, Wataru Taniguchi, Qi Yu Chen, Hidetoshi Saitoh, Qian Song, Ren Hao Liu, Kohei Koga, Tsuyoshi Matsuda, Yae Kaito-Sugimura, Jian Wang, Zhi Hua Li, Ya Cheng Lu, Kazuhide Inoue, Tsuda Makoto, Yun Qing Li, Terumasa Nakatsuka, Min Zhuo, Top-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex, Nature Communications, 10.1038/s41467-018-04309-2, 9, 1, 2018.05, [URL], Spinal sensory transmission is under descending biphasic modulation, and descending facilitation is believed to contribute to chronic pain. Descending modulation from the brainstem rostral ventromedial medulla (RVM) has been the most studied, whereas little is known about direct corticospinal modulation. Here, we found that stimulation in the anterior cingulate cortex (ACC) potentiated spinal excitatory synaptic transmission and this modulation is independent of the RVM. Peripheral nerve injury enhanced the spinal synaptic transmission and occluded the ACC-spinal cord facilitation. Inhibition of ACC reduced the enhanced spinal synaptic transmission caused by nerve injury. Finally, using optogenetics, we showed that selective activation of ACC-spinal cord projecting neurons caused behavioral pain sensitization, while inhibiting the projection induced analgesic effects. Our results provide strong evidence that ACC stimulation facilitates spinal sensory excitatory transmission by a RVM-independent manner, and that such top-down facilitation may contribute to the process of chronic neuropathic pain..
9. Tashima R, Koga K, Sekine M, Kanehisa K, Kohro Y, Tominaga K, Matsushita K, Tozaki-Saitoh H, Fukazawa Y, Inoue K, Yawo H, Furue H, Tsuda M, Optogenetic activation of non-nociceptive Aβ fibers induces neuropathic pain-like sensory and emotional behaviors after nerve injury in rats., eNeuro, 10.1523/ENEURO.0450-17.2018, 5, ENEURO.0450-17.2018, 2018.02.
10. Kohei Yoshihara, Tsuyoshi Matsuda, Yuta Koro, Hidetoshi Saitoh, Kazuhide Inoue, Tsuda Makoto, Astrocytic Ca2+ responses in the spinal dorsal horn by noxious stimuli to the skin, Journal of Pharmacological Sciences, 10.1016/j.jphs.2018.04.007, 2018.01, [URL], The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca2+ responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus..
11. Kensho Kanehisa, Miho Shiratori, Keisuke Koga, Hidetoshi Saitoh, Yuta Koro, Kenji Takamori, Tsuda Makoto, Specific activation of inhibitory interneurons in the spinal dorsal horn suppresses repetitive scratching in mouse models of chronic itch, Journal of Dermatological Science, 10.1016/j.jdermsci.2017.05.017, 88, 2, 251-254, 2017.11, [URL].
12. Ohgidani M, Kato TA, Hosoi M, Tsuda M, Hayakawa K, Hayaki C, Iwaki R, Sagata N, Hashimoto R, Inoue K, Sudo N, Kanba S, Fibromyalgia and microglial TNF-α: Translational research using human blood induced microglia-like cells., Sci Rep, 10.1038/s41598-017-11506-4, 7, 11882, 2017.09.
13. Koga K, Kanehisa K, Kohro Y, Shiratori-Hayashi M, Tozaki-Saitoh H, Inoue K, Furue H, Tsuda M, Chemogenetic silencing of GABAergic dorsal horn interneurons induces morphine-resistant spontaneous nocifensive behaviours., Sci Rep, 10.1038/s41598-017-04972-3, 7, 4739, 2017.07.
14. Hidetoshi Saitoh et al., P2Y12 receptors in primary microglia activate nuclear factor of activated T cell signaling to induce C-C chemokine 3 expression, J Neurochem, 141, 100-110, 2017.04.
15. Nakaya Michio et al., Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction, J Clin Invest, 127, 383-401 , 2017.01.
16. Matsunaga Naoya et al., Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease, EBioMedicine , S2352-3964, 30463-30467 , 2016.11.
17. Koyanagi S et al., Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia, Nat Commun, 7, 13102 , 2016.11.
18. Tomohiro Yamashita et al., Duloxetine inhibits microglial P2X4 receptor function and alleviates neuropathic pain after peripheral nerve injury, PLoS One, 11, e0165189 , 2016.10.
19. Matsumura Y et al., A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain, Sci Rep, 6, 32461, 2016.08.
20. Masuda T et al., Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain, Nat Commun, 7, 12529, 2016.08.
21. Tashima R et al., Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury, Sci Rep, 6, 23701, 2016.03.
22. Nishimura et al., Purinergic P2Y6 receptors heterodimerize with angiotensin AT1 receptors to promote angiotensin II-induced hypertension, Sci Signal, 9, ra7, 2016.01.
23. Yuta Kohro et al., A new minimally-invasive method for microinjection into the mouse spinal dorsal horn, Sci Rep, 5, 14306, 2015.09.
24. Miho Shiatori-Hayashi et al., STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch, NATURE MEDICINE, 10.1038/nm.3912, 21, 8, 927-931, 2015.08, Chronic itch is an intractable symptom of inflammatory skin diseases, such as atopic and contact dermatitis. Recent studies have revealed neuronal pathways selective for itch, but the mechanisms by which itch turns into a pathological chronic state are poorly understood. Using mouse models of atopic and contact dermatitis, we demonstrate a long-term reactive state of astrocytes in the dorsal horn of the spinal segments that corresponds to lesioned, itchy skin. We found that reactive astrogliosis depended on the activation of signal transducer and activator of transcription 3 (STAT3). Conditional disruption of astrocytic STAT3 suppressed chronic itch, and pharmacological inhibition of spinal STAT3 ameliorated the fully developed chronic itch. Mice with atopic dermatitis exhibited an increase in scratching elicited by intrathecal administration of the itch-inducer gastrin-releasing peptide (GRP), and this enhancement was normalized by suppressing STAT3-mediated reactive astrogliosis. Moreover, we identified lipocalin-2 (LCN2) as an astrocytic STAT3-dependent upregulated factor that was crucial for chronic itch, and we demonstrated that intrathecal administration of LCN2 to normal mice increased spinal GRP-evoked scratching. Our findings indicate that STAT3-dependent reactive astrocytes act as critical amplifiers of itching through a mechanism involving the enhancement of spinal itch signals by LCN2, thereby providing a previously unrecognized target for treating chronic itch..
25. Takahiro Masuda et al., Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia, J Pharmacol Sci, 128, 4, 216-220, 2015.08.
26. Igawa T et al., Solution structure of the rat P2X4 receptor head domain involved in inhibitory metal binding.
, FEBS Lett, 589, 680-686, 2015.03.
27. Akagi et al.,, Interferon regulatory factor 8 expressed in microglia contributes to tactile allodynia induced by repeated cold stress in rodents., J Pharmacol Sci, 121, 172-176, 2014.11.
28. Masuda Takahiro et al., IRF8 is a transcriptional determinant for microglial motility., Purinergic Signal, 10, 3, 515-521, 2014.09.
29. Yasui et al.,, A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation., Glia, 62, 9, 1407-1417, 2014.09.
30. Ohi-ishi et al.,, Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia., Mol Pain, 10, 53, 2014.08.
31. Matsushita K et al., Chemokine (C-C motif) receptor 5 is an important pathological regulator in the development and maintenance of neuropathic pain., Anesthesiology, 120, 6, 1491-1503, 2014.06.
32. Masuda Takahiro et al., Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain., Nat Commun, 5, 3771, 2014.05, 神経のダメージで発症する慢性的な痛み(神経障害性疼痛)の原因タンパク質として「IRF5」を突き止めました。IRF5は、神経の損傷後に脳・脊髄の免疫細胞であるミクログリアで増え、IRF5欠損マウスでは痛みが弱くなっていました。さらに、2003年にP2X4受容体タンパク質のミクログリアでの増加が神経障害性疼痛に重要であることを英国科学誌Natureで発表していますが、今回見つかったIRF5がP2X4受容体を増やす実行役であることも明らかにしました。この研究成果は、慢性疼痛メカニズムの解明へ向けた大きな前進となり、痛みを緩和する治療薬の開発に応用できることが期待されます(Nature Communications誌掲載)。.
33. Igawa T, Higashi S, yoshito abe, Takatoshi Ohkuri, Hiroyuki Tanaka, satoshi morimoto, 山下 智大, TSUDA MAKOTO, Kazuhide Inoue, Tadashi Ueda, Preparation and characterization of a monoclonal antibody against the refolded and functional extracellular domain of rat P2X4 receptor, JOURNAL OF BIOCHEMISTRY, 10.1093/jb/mvs143, 153, 3, 275-282, 2013.03.
34. Nakaya Michio, Tajima M, Kosako H, Nakaya T, Hashimoto A, Watari K, Nishihara H, Ohba M, Komiya S, Tani N, Motohiro Nishida, Taniguchi H, Sato Y, Matsumoto M, TSUDA MAKOTO, Kuroda M, Kazuhide Inoue, Hitoshi Kurose, GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance, NATURE COMMUNICATIONS, 10.1038/ncomms2540, 4, 1532, 2013.02.
35. Muratake H, Ito A, Toda T, Suzuki H, Fukasawa H, TSUDA MAKOTO, Kazuhide Inoue, Sugiyama K, Shudo K, (R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 10.1016/j.bmcl.2012.10.001, 22, 24, 7602-7604, 2012.12.
36. Sun L, Wu Z, Yoshinori Hayashi, Peters C, TSUDA MAKOTO, Kazuhide Inoue, Hiroshi Nakanishi, Microglial Cathepsin B Contributes to the Initiation of Peripheral Inflammation-Induced Chronic Pain, JOURNAL OF NEUROSCIENCE, 10.1523/JNEUROSCI.0677-12.2012, 32, 33, 11330-11342, 2012.08.
37. Uesugi A, Kataoka A, Tozaki-Saitoh H, Koga Y, Tsuda M, Robaye B, Boeynaems JM, Inoue K., Involvement of protein kinase D in uridine diphosphate-induced microglial macropinocytosis and phagocytosis., Glia, 60, 7, 1094-1105, 2012.07.
38. Toyomitsu E, Tsuda M, Yamashita T, Tozaki-Saitoh H, Tanaka Y, Inoue K., CCL2 promotes P2X4 receptor trafficking to the cell surface of microglia., Purinergic Signal., 8, 2, 301-310, 2012.06.
39. Masuda Takahiro, TSUDA MAKOTO, Ryohei Yoshinaga, Hidetoshi Saitoh, Keiko Ozato, Tomohiko Tamura, Kazuhide Inoue, IRF8 Is a Critical Transcription Factor for Transforming Microglia into a Reactive Phenotype, CELL REPORTS, 10.1016/j.celrep.2012.02.014, 1, 4, 334-340, 2012.04, 神経のダメージで発症する慢性的な激しい痛み(神経障害性疼痛)の原因タンパク質として「IRF8」を突き止めました。神経の損傷後,IRF8は脳・脊髄の免疫細胞と呼ばれる「ミクログリア」だけで劇的に増えており,同細胞の過度な活性化状態をつくりだして激しい痛みを引き起こすことを明らかにしました。また,IRF8は中枢神経においてミクログリア特異的に発現する転写因子として世界初の例であり,他の神経疾患においてもミクログリアの活性化が報告されていることから,他の領域にも本成果が波及することが期待できる。この研究成果は,慢性疼痛メカニズムの解明へ向けた大きな前進となり,痛みを緩和する治療薬の開発に応用できることが期待されます(Cell Reports誌掲載)。.
40. Kataoka A, Koga Y, Uesugi A, Tozaki-Saitoh H, Tsuda M, Inoue K., Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways., Purinergic Signal., 7, 4, 403-411, 2011.12.
41. Kuboyama K, Harada H, Tozaki-Saitoh H, Tsuda M, Ushijima K, Inoue K, Astrocytic P2Y1 receptor is involved in the regulation of cytokine/chemokine transcription and cerebral damage in a rat model of cerebral ischemia., J Cereb Blood Flow Metab, 10.1038/jcbfm.2011.49., 31, 9, 1930-1941, 2011.09.
42. Biber K*, Tsuda M*, Tozaki-Saitoh H*, Tsukamoto K, Toyomitsu E, Masuda T, Boddeke H, Inoue K. (*equal contributors), Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development., EMBO J, 30, 9, 1864-1873, 2011.05.
43. Tsuda M, Kohro Y, Yano T, Tsujikawa T, Kitano J, Tozaki-Saitoh H, Koyanagi S, Ohdo S, Ji RR, Salter MW, Inoue K, JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats., Brain, 134, 4, 1127-1139, 2011.04.
44. Maeda M, Tsuda M, Tozaki-Saitoh H, Inoue K, Kiyama H, Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn., Glia, 58, 15, 1838-1846, 2010.11.
45. Kusunose N, Koyanagi S, Hamamura K, Matsunaga N, Yoshida M, Uchida T, Tsuda M, Inoue K, Ohdo S, Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain. , Mol Pain, 6, 83, 2010.11.
46. Shiratori M, Tozaki-Saitoh H, Yoshitake M, Tsuda M, Inoue K, P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways., J Neurochem, 114, 3, 810-819, 2010.08.
47. Hasegawa S, Kohro Y, Shiratori M, Ishii S, Shimizu T, Tsuda M, Inoue K, Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain., PLoS ONE 5: e10467 (2010), 2010.05.
48. Tsuda M, Toyomitsu E, Kometani M, Tozaki-Saitoh H, Inoue K, Mechanisms underlying fibronectin-induced up-regulation of P2X4R expression in microglia: distinct roles of PI3K-Akt and MEK-ERK signalling pathways, J Cell Mol Med, 13, 9b, 3251-9, 2009.09.
49. Tsuda M, Kuboyama K, Inoue T, Nagata K, Tozaki-Saitoh H, Inoue K, Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays, Mol Pain, 5, 28, 2009.06.
50. Tsuda M, Masuda T, Kitano J, Shimoyama H, Tozaki-Saitoh H, Inoue K, IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain, Proc Natl Acad Sci U S A, 106, 19, 8032-8037, 2009.05.
51. Hasegawa S, Kohro Y, Tsuda M, Inoue K, Activation of cytosolic phospholipase A2 in dorsal root ganglion neurons by Ca2+/calmodulin-dependent protein kinase II after peripheral nerve injury, Mol Pain, 5, 22, 2009.05.
52. Shinozaki Y, Sumitomo K, Tsuda M, Koizumi S, Inoue K, Torimitsu K, Direct Observation of ATP-Induced Conformational Changes in Single P2X4 Receptors, PLoS Biol, 7, 5, e103, 2009.05.
53. Masuda J, Tsuda M, Tozaki-Saitoh H, Inoue K, Intrathecal delivery of PDGF produces tactile allodynia through its receptors in spinal microglia, Mol Pain, 5, 23, 2009.05.
54. Nagata K, Imai T, Yamashita T, Tsuda M, Tozaki-Saitoh H, Inoue K., Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief, Mol Pain, 5, 20, 2009.04.
55. Kataoka A, Tozaki-Saitoh H, Koga Y, Tsuda M, Inoue K, Activation of P2X7 receptors induces CCL3 production in microglial cells through transcription factor NFAT. , J Neurochem 108(1): 115-125 (2009), 2009.01.
56. Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K, P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury, J Neurosci 28: 4949-4956 (2008), 28: 4949-4956, 2008.05.
57. Tsuda M, Toyomitsu E, Komatsu T, Masuda T, Kunifusa E, Nasu-Tada K, Koizumi S, Yamamoto K, Ando J, Inoue K, Fibronectin/integrin system is involved in P2X(4) receptor upregulation in the spinal cord and neuropathic pain after nerve injury, Glia 56: 579-585 (2008), 2008.04.
58. Tsuda M, Ueno H, Kataoka A, Tozaki-Saitoh H, Inoue K, Activation of dorsal horn microglia contributes to diabetes-induced tactile allodynia via extracellular signal-regulated protein kinase signaling, Glia 56: 378-386 (2008), 2008.03.
59. Lyn tyrosine kinase is required for P2X4 receptor upregulation and neuropathic pain after peripheral nerve injury, Tsuda M, Tozaki-Saitoh H, Masuda T, Toyomitsu E, Tezuka T, Yamamoto T, Inoue K, Glia 56: 50-58 (2008), 2008.01.
60. Tsuda M, Hasegawa S, Inoue K, P2X receptors-mediated cytosolic phospholipase A2 activation in primary afferent sensory neurons contributes to neuropathic pain, J Neurochem 103: 1408-1416 (2007), 2007.11.
61. Tsuda M, Ishii S, Masuda T, Hasegawa S, Nakamura K, Nagata K, Yamashita T, Furue H, Tozaki-Saito H, Yoshimura M, Koizumi S, Shimizu T and Inoue K, Reduced pain behaviors and ERK activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet-activating factor receptor, J Neurochem 102: 1658–1668 (2007), 2007.09.
62. Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K., UDP acting at P2Y(6) receptors is a mediator of microglial phagocytosis., Nature. 446: 1091-1095 (2007), 2007.04.
63. Ikeda H, Tsuda M, Inoue K, Murase K., Long-term potentiation of neuronal excitation by neuron-glia interactions in the rat spinal dorsal horn., Eur J Neurosci. 2007 Mar;25(5):1297-306., 2007.03.
64. Tozaki-Saitoh H, Koizumi S, Sato Y, Tsuda M, Nagao T, Inoue K., Retinoic acids increase P2X2 receptor expression through the 5'-flanking region of P2rx2 gene in rat phaeochromocytoma PC-12 cells., Mol Pharmacol. 2006 Jul;70(1):319-28. , 2006.07.
65. Shiokawa H, Nakatsuka T, Furue H, Tsuda M, Katafuchi T, Inoue K, Yoshimura M., Direct excitation of deep dorsal horn neurones in the rat spinal cord by the activation of postsynaptic P2X receptors., J Physiol. 2006 Jun 15;573(Pt 3):753-63., 2006.06.
66. Nasu-Tada K, Koizumi S, Tsuda M, Kunifusa E, Inoue K., Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglial P2X4, a key molecule for mechanical allodynia., Glia. 2006 May;53(7):769-75., 2006.05.
67. Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y., BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain., Nature. 2005 Dec 15;438(7070):1017-21. , 10.1038/nature04223, 438, 7070, 1017-1021, 2005.12.
68. Narita M, Miyatake M, Shibasaki M, Tsuda M, Koizumi S, Narita M, Yajima Y, Inoue K, Suzuki T., Long-lasting change in brain dynamics induced by methamphetamine: enhancement of protein kinase C-dependent astrocytic response and behavioral sensitization., J Neurochem. 2005 Jun;93(6):1383-92., 2005.06.
69. Koizumi S, Fujishita K, Inoue K, Shigemoto-Mogami Y, Tsuda M, Inoue K., Ca2+ waves in keratinocytes are transmitted to sensory neurons: the involvement of extracellular ATP and P2Y2 receptor activation., Biochem J. 2004 Jun 1;380(Pt 2):329-38., 10.1042/BJ20031089, 380, 329-338, 2004.06.
70. Tsuda M, Mizokoshi A, Shigemoto-Mogami Y, Koizumi S, Inoue K., Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury., Glia. 2004 Jan 1;45(1):89-95., 10.1002/glia.10308, 45, 1, 89-95, 2004.01.
71. Inoue K, Koizumi S, Tsuda M, Shigemoto-Mogami Y., Signaling of ATP receptors in glia-neuron interaction and pain., Life Sci. 2003 Dec 5;74(2-3):189-97., 10.1016/j.lfs.2003.09.006, 74, 2-3, 189-197, 2003.12.
72. Koizumi S, Fujishita K, Tsuda M, Shigemoto-Mogami Y, Inoue K., Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures., Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11023-8., 10.1073/pnas.1834448100, 100, 19, 11023-11028, 2003.09.
73. Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, Salter MW, Inoue K. Related Articles, Links , P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury., Nature. 2003 Aug 14;424(6950):778-83., 10.1038/nature01786, 424, 6950, 778-783, 2003.08.
74. Tsuda M, Shigemoto-Mogami Y, Ueno S, Koizumi S, Ueda H, Iwanaga T, Inoue K., Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain., Eur J Neurosci. 2002 May;15(9):1444-50., 10.1046/j.1460-9568.2002.01982.x, 15, 9, 1444-1450, 2002.05.
75. Shigemoto-Mogami Y, Koizumi S, Tsuda M, Ohsawa K, Kohsaka S, Inoue K., Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5., J Neurochem. 2001 Sep;78(6):1339-49., 10.1046/j.1471-4159.2001.00514.x, 78, 6, 1339-1349, 2001.09.
76. Tsuda M, Koizumi S, Inoue K., Role of endogenous ATP at the incision area in a rat model of postoperative pain.
, Neuroreport. 2001 Jun 13;12(8):1701-4., 10.1097/00001756-200106130-00036, 12, 8, 1701-1704, 2001.06.
77. Yajima Y, Narita M, Tsuda M, Imai S, Kamei J, Nagase H, Suzuki T., Modulation of NMDA- and (+)TAN-67-induced nociception by GABA(B) receptors in the mouse spinal cord., Life Sci. 2000 Dec 29;68(6):719-25., 2000.12.
78. Tsuda M, Koizumi S, Kita A, Shigemoto Y, Ueno S, Inoue K., Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons., J Neurosci. 2000 Aug 1;20(15):RC90., 20, 15, 2000.08.
79. Suzuki T, Kato H, Aoki T, Tsuda M, Narita M, Misawa M., Effects of the non-competitive NMDA receptor antagonist ketamine on morphine-induced place preference in mice., Life Sci. 2000 Jun 16;67(4):383-9., 2000.06.
80. Tsuda M, Ueno S, Inoue K., Evidence for the involvement of spinal endogenous ATP and P2X receptors in nociceptive responses caused by formalin and capsaicin in mice.
, Br J Pharmacol. 1999 Dec;128(7):1497-504.
, 1999.12.
81. Tsuda M, Ueno S, Inoue K., In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system., Br J Pharmacol. 1999 May;127(2):449-56., 1999.05.
82. Suzuki T, Shimizu N, Tsuda M, Soma M, Misawa M., Role of metabotropic glutamate receptors in the hypersusceptibility to pentylenetetrazole-induced seizure during diazepam withdrawal.
, Eur J Pharmacol. 1999 Mar 19;369(2):163-8., 1999.03.
83. Suzuki T, Kato H, Tsuda M, Suzuki H, Misawa M., Effects of the non-competitive NMDA receptor antagonist ifenprodil on the morphine-induced place preference in mice.
, Life Sci. 1999;64(12):PL151-6., 1999.02.
84. Ueno S, Tsuda M, Iwanaga T, Inoue K., Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons., Br J Pharmacol. 1999 Jan;126(2):429-36., 1999.01.
85. Tsuda M, Suzuki T, Misawa M., NMDA receptor antagonists potently suppress the spontaneous withdrawal signs induced by discontinuation of long-term diazepam treatment in Fischer 344 rats.
, Brain Res. 1998 Apr 20;790(1-2):82-90., 1998.04.
86. Tsuda M, Shimizu N, Yajima Y, Suzuki T, Misawa M., Hypersusceptibility to DMCM-induced seizures during diazepam withdrawal in mice: evidence for upregulation of NMDA receptors.
, Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):309-15., 1998.03.
87. Tsuda M, Suzuki T, Misawa M., Subsensitivity to mitochondrial diazepam binding inhibitor receptor agonist FGIN-1-27-induced antiseizure effect in diazepam-withdrawn mice., Life Sci. 1998;62(14):PL213-7., 1998.02.
88. Tsuda M, Shimizu N, Yajima Y, Suzuki T, Misawa M., Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice.
, Eur J Pharmacol. 1998 Feb 26;344(1):27-30., 1998.02.
89. Tsuda M, Suzuki T, Misawa M., Region-specific changes in [3H]dizocilpine binding in diazepam-withdrawn rats.
, Neurosci Lett. 1998 Jan 9;240(2):113-5., 1998.01.
90. Tsuda M, Chiba Y, Suzuki T, Misawa M., Upregulation of NMDA receptor subunit proteins in the cerebral cortex during diazepam withdrawal.
, Eur J Pharmacol. 1998 Jan 12;341(2-3):R1-2. , 1998.01.
91. Tsuda M, Suzuki T, Misawa M., Age-related decrease in the antiseizure effect of ifenprodil against pentylenetetrazole in mice.
, Brain Res Dev Brain Res. 1997 Dec 19;104(1-2):201-4., 1997.12.
92. Tsuda M, Suzuki T, Misawa M., Aggravation of DMCM-induced seizure by nitric oxide synthase inhibitors in mice., Life Sci. 1997;60(23):PL339-43., 1997.05.
93. Kamei J, Sodeyama M, Tsuda M, Suzuki T, Nagase H., Antinociceptive effect of buprenorphine in mu1-opioid receptor deficient CXBK mice., Life Sci. 1997;60(22):PL 333-7., 1997.04.
94. Tsuda M, Suzuki T, Misawa M., Recovery of decreased seizure threshold for pentylenetetrazole during diazepam withdrawal by NMDA receptor antagonists.
, Eur J Pharmacol. 1997 Apr 11;324(1):63-6., 1997.04.
95. Tsuda M, Suzuki T, Misawa M., Role of the NMDA receptor complex in DMCM-induced seizure in mice., Neuroreport. 1997 Feb 10;8(3):603-6., 1997.02.
96. Suzuki T, Ise Y, Tsuda M, Maeda J, Misawa M., Mecamylamine-precipitated nicotine-withdrawal aversion in rats., Eur J Pharmacol. 1996 Oct 31;314(3):281-4., 1996.10.
97. Tsuda M, Suzuki T, Misawa M, Nagase H., Involvement of the opioid system in the anxiolytic effect of diazepam in mice., Eur J Pharmacol. 1996 Jun 20;307(1):7-14., 1996.06.
98. Suzuki T, Tsuda M, Narita M, Funada M, Mizoguchi H, Misawa M., Diazepam pretreatment suppresses morphine withdrawal signs in the mouse., Life Sci. 1996;58(4):349-57., 1995.12.
99. Suzuki T, Tsuda M, Funada M, Misawa M., Blockade of morphine-induced place preference by diazepam in mice., Eur J Pharmacol. 1995 Jul 14;280(3):327-30., 1995.07.
100. Mizoguchi H, Shirayama N, Tsuda M, Yoshiike M, Suzuki T, Misawa M., Potentiation of physical dependence on diazepam by ondansetron in rats., Life Sci. 1994;54(9):PL131-6., 1994.07.

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