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Anti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats.
Ishikura, Teruyuki; Kinoshita, Makoto; Shimizu, Mikito; Yasumizu, Yoshiaki; Motooka, Daisuke; Okuzaki, Daisuke; Yamashita, Kazuya; Murata, Hisashi; Beppu, Shohei; Koda, Toru; Tada, Satoru; Shiraishi, Naoyuki; Sugiyama, Yasuko; Miyamoto, Katsuichi; Kusunoki, Susumu; Sugimoto, Tomoyuki; Kumanogoh, Atsushi; Okuno, Tatsusada; Mochizuki, Hideki.
Afiliação
  • Ishikura T; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Kinoshita M; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. mkinoshita@neurol.med.osaka-u.ac.jp.
  • Shimizu M; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Yasumizu Y; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Motooka D; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
  • Okuzaki D; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
  • Yamashita K; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Murata H; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Beppu S; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Koda T; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Tada S; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Shiraishi N; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Sugiyama Y; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • Miyamoto K; Department of Neurology, Kindai University Faculty of Medicine, Sayama, Osaka, Japan.
  • Kusunoki S; Department of Neurology, Kindai University Faculty of Medicine, Sayama, Osaka, Japan.
  • Sugimoto T; Graduate School of Data Science, Shiga University, Hikone, Shiga, Japan.
  • Kumanogoh A; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Okuno T; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. okuno@neurol.med.osaka-u.ac.jp.
  • Mochizuki H; Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Neuroinflammation ; 18(1): 181, 2021 Aug 21.
Article em En | MEDLINE | ID: mdl-34419102
BACKGROUND: Intractable neuropathic pain is a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. In this study, we focused on ATP, which is one of the damage-associated molecular patterns, and also a well-recognized molecule involved in peripheral neuropathic pain. METHODS: We assessed the development of pain symptoms by injecting anti-AQP4 recombinant autoantibodies (rAQP4 IgG) into rat spinal cords. We incubated HEK293 cells expressing AQP4 (HEK-AQP4) and rat astrocytes with rAQP4 IgG and assessed the level of ATP in the supernatant. We performed transcriptome analysis of the spinal cords injected with rAQP4 IgG. Pharmacological inhibition was also applied to investigate the involvement of ATP in the development of neuropathic pain in our rat model. The ATP concentration within the cerebrospinal fluid was examined in patients with NMOSD and other neurological diseases. RESULTS: Development of mechanical allodynia was confirmed in rAQP4 IgG-treated rats. AQP4-Ab-mediated extracellular ATP release from astrocytes was observed in vitro, and pharmacological inhibition of ATP receptor reversed mechanical allodynia in the rAQP4 IgG-treated rats. Furthermore, transcriptome analysis revealed elevation of gene expressions related to several ATP receptors including P2rx4 and IL1B in the spinal cord of rAQP4 IgG-treated rats. In patients, CSF ATP concentration was significantly higher in the acute and remission phase of NMOSD than in multiple sclerosis or other neurological disorders. CONCLUSION: Anti-AQP4 antibody was shown to induce the release of extracellular ATP from astrocytes. The ATP-mediated development of mechanical allodynia was also suggested in rats treated with anti-AQP4 antibody. Our study indicates the pivotal role of ATP in the pain mechanism of NMOSD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autoanticorpos / Trifosfato de Adenosina / Astrócitos / Neuromielite Óptica / Aquaporina 4 / Neuralgia Limite: Animals / Humans Idioma: En Revista: J Neuroinflammation Assunto da revista: NEUROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autoanticorpos / Trifosfato de Adenosina / Astrócitos / Neuromielite Óptica / Aquaporina 4 / Neuralgia Limite: Animals / Humans Idioma: En Revista: J Neuroinflammation Assunto da revista: NEUROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Japão