{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:40:21Z","timestamp":1792730421470,"version":"4.5.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,3,27]]},"abstract":"<jats:p>\n                    In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spikes through alterations in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spike frequency by stimulating internal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spike frequency and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1120747109","type":"journal-article","created":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T01:00:12Z","timestamp":1331600412000},"page":"5057-5062","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca\n                    <sup>2+<\/sup>\n                    spike frequency"],"prefix":"10.1073","volume":"109","author":[{"given":"Jennifer K.","family":"Fahrion","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Komuro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Littner","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Raoult","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit 982, Diff\u00e9renciation et Communication Neuronale et Neuroendocrine, University of Rouen, Mont-Saint-Aignan, 76821 France; and"},{"name":"Cell Imaging Platform of Normandy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institute for Research and Innovation in Biomedicine, University of Rouen, Mont-Saint-Aignan, 76821 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Galas","sequence":"additional","affiliation":[{"name":"Cell Imaging Platform of Normandy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institute for Research and Innovation in Biomedicine, University of Rouen, Mont-Saint-Aignan, 76821 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vaudry","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit 982, Diff\u00e9renciation et Communication Neuronale et Neuroendocrine, University of Rouen, Mont-Saint-Aignan, 76821 France; and"},{"name":"Cell Imaging Platform of Normandy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institute for Research and Innovation in Biomedicine, University of Rouen, Mont-Saint-Aignan, 76821 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Komuro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,3,12]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"426","article-title":"Neuropsychiatric disturbances due to organic mercury poisoning during the prenatal period","volume":"66","author":"Harada M","year":"1964","unstructured":"M Harada, Neuropsychiatric disturbances due to organic mercury poisoning during the prenatal period. 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