{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:50:35Z","timestamp":1779119435403,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,9,26]],"date-time":"2001-09-26T00:00:00Z","timestamp":1001462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2001,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We reported previously that BDNF induced glutamate release was dependent on intracellular Ca<jats:sup>2+<\/jats:sup> but not extracellular Ca<jats:sup>2+<\/jats:sup> in cerebellar neurons (Numakawa et al., <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib33\">1999<\/jats:ext-link>). It was revealed that the release was through a non\u2010exocytotic pathway (Takei et al., <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib46\">1998<\/jats:ext-link>; Numakawa et al., <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib33\">1999<\/jats:ext-link>). In the present study, we monitored the dynamics of intracellular Ca<jats:sup>2+<\/jats:sup> and Na<jats:sup>+<\/jats:sup> in cerebellar neurons, and investigated the possibility of reverse transport of glutamate mediated by BDNF. As reported, BDNF increased the intracellular Ca<jats:sup>2+<\/jats:sup> level. We found that the Ca<jats:sup>2+<\/jats:sup> increase induced by BDNF was completely blocked by xestospongin C, an IP<jats:sub>3<\/jats:sub> receptor antagonist, and U\u201073122, a PLC\u2010\u03b3 inhibitor. Xestospongin C and U\u201073122 also blocked the BDNF\u2010dependent glutamate release, suggesting that the BDNF\u2010induced transient increase of Ca<jats:sup>2+<\/jats:sup> through the activation of the PLC\u2010\u03b3\/ IP<jats:sub>3<\/jats:sub> pathway was essential for the glutamate release. We found that BDNF induced a Na<jats:sup>+<\/jats:sup> influx. This was blocked by treatment with TTX. U\u201073122 and xestospongin C blocked the BDNF\u2010induced Na<jats:sup>+<\/jats:sup> influx, suggesting that the Na<jats:sup>+<\/jats:sup>influx required the BDNF\u2010induced Ca<jats:sup>2+<\/jats:sup> increase. Next, we examined the possibility that a co\u2010transporter of Na<jats:sup>+<\/jats:sup> and glutamate was involved in the BDNF\u2010induced glutamate release. BDNF\u2010induced glutamate release was blocked by L\u2010trans\u2010pyrollidine\u20102,4\u2010dicalboxylic acid (t\u2010PDC), a glutamate transporter inhibitor, whereas neither the 4\u2010aminopyridine (4AP)\u2010 nor high potassium (HK<jats:sup>+<\/jats:sup>)\u2010induced release was blocked by t\u2010PDC. In addition, DL\u2010threo\u2010\u03b2\u2010benzyloxyaspartate (DL\u2010TBOA) also blocked the BDNF\u2010mediated glutamate release, suggesting that reverse transport of glutamate may be involved. All the results therefore suggest that Na<jats:sup>+<\/jats:sup>\u2010dependent reverse transport contributes to BDNF\u2010mediated transmitter release through the PLC\u2010\u03b3\/IP<jats:sub>3<\/jats:sub>\u2010mediated Ca<jats:sup>2+<\/jats:sup> signaling. J. Neurosci. Res. 66:96\u2013108, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.1201","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T19:53:55Z","timestamp":1030305235000},"page":"96-108","source":"Crossref","is-referenced-by-count":51,"title":["Brain\u2010derived neurotrophic factor triggers a rapid glutamate release through increase of intracellular Ca<sup>2+<\/sup> and Na<sup>+<\/sup> in cultured cerebellar neurons"],"prefix":"10.1002","volume":"66","author":[{"given":"T.","family":"Numakawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Yokomaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Takei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Hatanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,9,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-17-06707.1997"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199309150-00004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(96)80115-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/7258"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3145"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)80016-U"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)90033-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/381706a0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.6.3.243"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(99)01532-5"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(88)90069-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/16711"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80225-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90927-X"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/44847"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199511270-00020"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/360467a0"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7886457"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480251108"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199305000-00005"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1523\/JNEUROSCI.19-07-02580.1999","article-title":"Optical detection of synaptically induced glutamate transport in hippocampal slices","volume":"19","author":"Kojima S","year":"1999","journal-title":"J Neurosci"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.19.8856"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.22.12547"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(94)00220-T"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199412300-00007"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.8074"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10231.1998"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10884"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80838-7"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2333512"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00393.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01867-3"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(00)00103-6"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00335.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80140-3"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/360464a0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.1523\/JNEUROSCI.19-12-04972.1999","article-title":"Impairments in high\u2010frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice","volume":"19","author":"Pozzo Miller LD","year":"1999","journal-title":"J Neurosci"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.53.3.438"},{"key":"e_1_2_7_40_1","first-page":"169","article-title":"Heterogeneity and functional properties of subtypes of sodium\u2010dependent glutamate transporters in the mammalian central nervous system","volume":"37","author":"Robinson MB","year":"1997","journal-title":"Adv Pharmacol"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01052-4"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90158-N"},{"key":"e_1_2_7_43_1","doi-asserted-by":"crossref","first-page":"7025","DOI":"10.1523\/JNEUROSCI.19-16-07025.1999","article-title":"Long\u2010term enhancement of central synaptic transmission by chronic brain\u2010derived neurotrophic factor treatment","volume":"19","author":"Sherwood NT","year":"1999","journal-title":"J Neurosci"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.53.2.195"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10955"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.42.27620"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5236.593"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.5.955"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01345.x"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/82858"},{"key":"e_1_2_7_51_1","first-page":"145","article-title":"Biochemical and pharmacologic studies with KT7692 and LY294002 on the role of phosphatidylinositol 3\u2010kinase in Fc epsilon RI\u2010mediated signal transduction","volume":"312","author":"Yano H","year":"1995","journal-title":"J Biol Chem"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/383634a0"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020050155"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.1201","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.1201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T03:42:51Z","timestamp":1696909371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.1201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,26]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001,10]]}},"alternative-id":["10.1002\/jnr.1201"],"URL":"https:\/\/doi.org\/10.1002\/jnr.1201","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,26]]}}}