{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:30:24Z","timestamp":1790163024033,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2007,6,27]],"date-time":"2007-06-27T00:00:00Z","timestamp":1182902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Positron emission tomography (PET) is a useful technique for the consecutive investigation of the relationship between changes in neurotransmission biomarkers and behavioral signs in animal models of Parkinson's disease (PD). In this study, we aimed to investigate the threshold of dopamine (DA) neuron damage for the appearance of tremor by observing the longitudinal changes of pre\u2010 and post\u2010synaptic DA biomarkers in awake monkeys using PET with multiple tracers. Three cynomolgus monkeys were treated with MPTP every 3\u20136 weeks until tremor was observed. Brain uptake of [<jats:sup>11<\/jats:sup>C]PE2I, [\u03b2\u2010<jats:sup>11<\/jats:sup>C]DOPA, and [<jats:sup>11<\/jats:sup>C]raclopride for DA transporter (DAT), DOPA utilization, and DA D2 receptor were measured using PET as a single set in awake condition. Sets of PET scans were repeated in parallel with continuous behavioral estimation. The pre\u2010synaptic biomarkers of DA neuron in the striatum decreased [<jats:sup>11<\/jats:sup>C]PE2I binding and [\u03b2\u2010<jats:sup>11<\/jats:sup>C]DOPA uptake in an MPTP dose\u2010dependent manner. Tremor was not observed until striatal [<jats:sup>11<\/jats:sup>C]PE2I binding was reduced to about 15% of the pretreatment level and [\u03b2\u2010<jats:sup>11<\/jats:sup>C]DOPA uptake was reduced to about 34%. DA D2 receptor measured by [<jats:sup>11<\/jats:sup>C]raclopride was not significantly changed throughout the experiment. Our results revealed that it is possible to quantitatively define the threshold of the onset of behavioral PD signs by monitoring spontaneous motor activity, and in vivo PET with DAT marker can be a biomarker for early diagnosis at the presymptomatic stage of PD and for high\u2010risk groups. Synapse 61:809\u2013819, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.20431","type":"journal-article","created":{"date-parts":[[2007,6,27]],"date-time":"2007-06-27T19:21:41Z","timestamp":1182972101000},"page":"809-819","source":"Crossref","is-referenced-by-count":23,"title":["Progressive changes of pre\u2010 and post\u2010synaptic dopaminergic biomarkers in conscious MPTP\u2010treated cynomolgus monkeys measured by positronemission tomography"],"prefix":"10.1002","volume":"61","author":[{"given":"Yuji","family":"Nagai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Obayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoki","family":"Inaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Okauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Suhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,6,27]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.7.1325"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-17-06853.2001"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310209"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.14.4546"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/317246a0"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(01)00425-3"},{"key":"e_1_2_1_9_1","first-page":"167","article-title":"Determination and visualization of damage to striatal dopaminergic terminals in 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010induced parkinsonism by [18F]\u2010labeled 6\u2010fluoro\u2010L\u2010dopa and positron emission tomography","volume":"45","author":"Chiueh CC","year":"1987","journal-title":"Adv Neurol"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.8.1437"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8257(199911)14:6<1025::AID-MDS1020>3.0.CO;2-P"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/NP.1993.27"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199807)29:3<225::AID-SYN4>3.0.CO;2-8"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(200011)38:2<105::AID-SYN1>3.0.CO;2-S"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.10070"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2007.00818.x"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(88)90575-7"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1987.tb05629.x"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400609"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1091"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1090"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340331"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(91)90073-Q"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199108000-00008"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(97)00224-2"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.6.1578"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.17.5.427"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(99)00184-3"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.3727\/000000005783982684"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90599-L"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-005-0027-9"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890090107"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198804073181402"},{"issue":"4","key":"e_1_2_1_35_1","first-page":"27","article-title":"When does Parkinson's disease begin?","volume":"42","author":"Koller WC","year":"1992","journal-title":"Neurology"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002590050254"},{"key":"e_1_2_1_37_1","first-page":"1263","article-title":"PET studies on brain monoamine transporters with carbon\u201011\u2010\u03b2\u2010CIT in Parkinson's disease","volume":"36","author":"Laihinen AO","year":"1995","journal-title":"J Nucl Med"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1996.0066"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200004)47:4<493::AID-ANA13>3.0.CO;2-4"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1972.tb05099.x"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:28:3:209"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90601-G"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1991.154"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0167"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199611)24:3<262::AID-SYN9>3.0.CO;2-C"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0878"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.1063"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1985.87"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00163-0"},{"key":"e_1_2_1_50_1","first-page":"663","article-title":"Quantification of dopamine transporter by 123I\u2010PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease","volume":"44","author":"Prunier C","year":"2003","journal-title":"J Nucl Med"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.4.580"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01249445"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1991.tb05026.x"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870080203"},{"key":"e_1_2_1_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890210202"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8043(99)00118-9"},{"key":"e_1_2_1_57_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.7.1292"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.3.313"},{"key":"e_1_2_1_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200202000-00011"},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(90)90003-Y"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1992.tb04005.x"},{"key":"e_1_2_1_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1992.tb04021.x"},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410308"},{"key":"e_1_2_1_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199910000-00011"},{"key":"e_1_2_1_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(200008)37:2<95::AID-SYN3>3.0.CO;2-H"},{"key":"e_1_2_1_66_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.3.717"},{"key":"e_1_2_1_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360513"},{"key":"e_1_2_1_68_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1994.1069"},{"key":"e_1_2_1_69_1","doi-asserted-by":"publisher","DOI":"10.2169\/naika.77.1378"}],"container-title":["Synapse"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsyn.20431","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/syn.20431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T12:30:05Z","timestamp":1700051405000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/syn.20431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6,27]]},"references-count":68,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["10.1002\/syn.20431"],"URL":"https:\/\/doi.org\/10.1002\/syn.20431","archive":["Portico"],"relation":{},"ISSN":["0887-4476","1098-2396"],"issn-type":[{"value":"0887-4476","type":"print"},{"value":"1098-2396","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6,27]]}}}