{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:25:52Z","timestamp":1783412752652,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,6,13]],"date-time":"2014-06-13T00:00:00Z","timestamp":1402617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["P50 NS071669"],"award-info":[{"award-number":["P50 NS071669"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In Parkinson's disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>), profound putamen dopamine (<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>) depletion reflects denervation and a shift from vesicular sequestration to oxidative deamination of cytoplasmic<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>in residual terminals.<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>also involves cardiac sympathetic denervation. Whether<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>entails myocardial norepinephrine (<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>) depletion and a sequestration\u2013deamination shift have been unknown. We measured apical myocardial tissue concentrations of<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>, and their neuronal metabolites 3,4\u2010dihydroxyphenylglycol (<jats:styled-content style=\"fixed-case\">DHPG<\/jats:styled-content>), and 3,4\u2010dihydroxyphenylacetic acid (<jats:styled-content style=\"fixed-case\">DOPAC<\/jats:styled-content>) from 23<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>patients and 23 controls and ascertained the extent of myocardial<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>depletion in<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. We devised, validated in<jats:styled-content style=\"fixed-case\">VMAT<\/jats:styled-content>2\u2010Lo mice, and applied 5 neurochemical indices of the sequestration\u2013deamination shift\u2014concentration ratios of<jats:styled-content style=\"fixed-case\">DOPAC<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">DHPG<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">DOPAC<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>, and<jats:styled-content style=\"fixed-case\">DHPG<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">DOPAC<\/jats:styled-content>\u2014and used a kinetic model to estimate the extent of the vesicular storage defect. The<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>group had decreased myocardial<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>content (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001). The majority of patients (70%) had severe<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>depletion (mean 2% of control), and in this subgroup all five indices of a sequestration\u2013deamination shift were increased compared to controls (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001 for each). Vesicular storage in residual nerves was estimated to be decreased by 84\u201391% in this subgroup. We conclude that most<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>patients have severe myocardial<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>depletion, because of both sympathetic denervation and decreased vesicular storage in residual nerves.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12766-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>We found that the majority (70%) of Parkinson's disease (PD) patients have profound (98%) myocardial norepinephrine depletion, because of both cardiac sympathetic denervation and a shift from vesicular sequestration to oxidative deamination of cytoplasmic catecholamines in the residual nerves. This shift may be part of a final common pathogenetic pathway in the loss of catecholaminergic neurons that characterizes PD.<\/jats:p>","DOI":"10.1111\/jnc.12766","type":"journal-article","created":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T08:55:28Z","timestamp":1400748928000},"page":"219-228","source":"Crossref","is-referenced-by-count":34,"title":["A vesicular sequestration to oxidative deamination shift in myocardial sympathetic nerves in Parkinson's disease"],"prefix":"10.1111","volume":"131","author":[{"given":"David S.","family":"Goldstein","sequence":"first","affiliation":[{"name":"Clinical Neurocardiology Section CNP\/DIR\/NINDS\/NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Clinical Neurocardiology Section CNP\/DIR\/NINDS\/NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Holmes","sequence":"additional","affiliation":[{"name":"Clinical Neurocardiology Section CNP\/DIR\/NINDS\/NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Miller","sequence":"additional","affiliation":[{"name":"School of Public Health Environmental Health Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehonatan","family":"Sharabi","sequence":"additional","affiliation":[{"name":"Hypertension Unit Chaim Sheba Medical Center and Tel Aviv University Tel\u2010HaShomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irwin J.","family":"Kopin","sequence":"additional","affiliation":[{"name":"Clinical Neurocardiology Section CNP\/DIR\/NINDS\/NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2005.tb00097.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-0956-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0303-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0319-07.2007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1971.03190260019005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24921"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0665-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01485901"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.9.1667"},{"key":"e_1_2_8_11_1","first-page":"949","volume-title":"Stress: Molecular, Genetic and Neurobiological Advances","author":"Eisenhofer G.","year":"1996"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.3.1"},{"key":"e_1_2_8_13_1","first-page":"E284","article-title":"Dopa, norepinephrine, and dopamine in rat tissues: no effect of sympathectomy on muscle dopa","volume":"256","author":"Eldrup E.","year":"1989","journal-title":"Am. 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