{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:13:10Z","timestamp":1787015590897,"version":"build-2736575974"},"reference-count":70,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T00:00:00Z","timestamp":1386115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"crossref","award":["135179"],"award-info":[{"award-number":["135179"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"crossref","award":["127150"],"award-info":[{"award-number":["127150"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Russian Foundation for Basic Research","award":["11-04-00397"],"award-info":[{"award-number":["11-04-00397"]}]},{"name":"Russian Foundation for Basic Research","award":["14-04-31707"],"award-info":[{"award-number":["14-04-31707"]}]},{"name":"Russian Foundation for Basic Research","award":["14-04-00227"],"award-info":[{"award-number":["14-04-00227"]}]},{"DOI":"10.13039\/501100003443","name":"Russian Federation Ministry of Education and Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent studies suggested contribution of homocysteine (HCY) to neurodegenerative disorders and migraine. However, HCY effect in the nociceptive system is essentially unknown. To explore the mechanism of HCY action, we studied short\u2010 and long\u2010term effects of this amino acid on rat peripheral and central neurons. HCY induced intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients in cultured trigeminal neurons and satellite glial cells (SGC), which were blocked by the NMDA antagonist AP\u20105 in neurons, but not in SGCs. In contrast, 3\u2010((2\u2010Methyl\u20104\u2010thiazolyl)ethynyl)pyridine (MTEP), the metabotropic mGluR5 (metabotropic glutamate receptor 5 subtype) antagonist, preferentially inhibited Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients in SGCs. Prolonged application of HCY induced apoptotic cell death of both kinds of trigeminal cells. The apoptosis was blocked by AP\u20105 or by the mGluR5 antagonist MTEP. Likewise, in cortical neurons, HCY\u2010induced cell death was inhibited by AP\u20105 or MTEP. Imaging with 2\u2032,7\u2032\u2010dichlorodihydrofluorescein diacetate or mitochondrial dye Rhodamine\u2010123 as well as thiobarbituric acid reactive substances assay did not reveal involvement of oxidative stress in the action of HCY. Thus, elevation of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    by HCY in neurons is mediated by NMDA and mGluR5 receptors while SGC are activated through the\n                    <jats:styled-content style=\"fixed-case\">mG<\/jats:styled-content>\n                    luR5 subtype. Long\u2010term neurotoxic effects in peripheral and central neurons involved both receptor types. Our data suggest glutamatergic mechanisms of HCY\u2010induced sensitization and apoptosis of trigeminal nociceptors.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12615-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>\n                  <jats:p>\n                    We show that NMDA and mGluR5 receptors in trigeminal and cortical neurons and mGluR5 receptors in glial cells mediate homocysteine (HCY)\u2010induced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    elevation whereas HCY\u2010evoked apoptosis involves both NMDA and mGluR5 receptors. This study revealed migraine\u2010related short\u2010 and long\u2010term effects of this redox active aminoacid within the nociceptive system and highlights potential targets for anti\u2010nociception and neuroprotection.\n                  <\/jats:p>","DOI":"10.1111\/jnc.12615","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T05:55:18Z","timestamp":1385358918000},"page":"264-274","source":"Crossref","is-referenced-by-count":74,"title":["The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells"],"prefix":"10.1111","volume":"129","author":[{"given":"Polina A.","family":"Abushik","sequence":"first","affiliation":[{"name":"Department of Neurobiology A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"},{"name":"Laboratory of Comparative Physiology of Cerebellum Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Science Saint\u2010Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Niittykoski","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"},{"name":"Biotechnology and Molecular Medicine A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raisa","family":"Giniatullina","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Shakirzyanova","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Bart","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy","family":"Fayuk","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry A.","family":"Sibarov","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Physiology of Cerebellum Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Science Saint\u2010Petersburg Russia"},{"name":"Laboratory of Molecular Neurodegeneration Saint\u2010Petersburg State Polytechnic University Saint\u2010Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei M.","family":"Antonov","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Physiology of Cerebellum Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Science Saint\u2010Petersburg Russia"},{"name":"Laboratory of Molecular Neurodegeneration Saint\u2010Petersburg State Polytechnic University Saint\u2010Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Giniatullin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. 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