{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:33:51Z","timestamp":1790800431455,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T00:00:00Z","timestamp":1464825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004807","name":"California Department of Fish and Game","doi-asserted-by":"publisher","award":["BI1551\/2\u20101"],"award-info":[{"award-number":["BI1551\/2\u20101"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Neuromelanin (NM) is a compound which highly accumulates mainly in catecholamine neurons of the substantia nigra (SN), and is contained in organelles (NM\u2010containing organelles) with lipid bodies and proteins. These neurons selectively degenerate in Parkinson's disease and NM can play either a protective or toxic role. NM\u2010containing organelles of SN were investigated by Analytical Electron Microscopy (AEM) and Nano\u2010Secondary Ion Mass Spectrometry (NanoSIMS) within human tissue sections with respect to ultrastructure and elemental composition. Within the NM\u2010containing organelle, the single NM granules and lipid bodies had sizes of about 200\u2013600\u00a0nm. Energy\u2010Dispersive X\u2010ray microanalysis spectra of the NM granules and lipid bodies were acquired with 100\u00a0nm beam diameter in AEM, NanoSIMS yielded elemental maps with a lateral resolution of about 150\u00a0nm. AEM yielded the quantitative elemental composition of NM granules and bound metals, e.g., iron with a mole fraction of about 0.15 atomic percent. Chemical analyses by AEM and NanoSIMS were consistent at the subcellular level so that nanoSIMS measurements have been quantitated. In NM granules of SN from healthy subjects, a significant amount of S, Fe, and Cu was found. In lipid bodies an amount of P consistent with the presence of phospholipids was measured. The improved detection limits of nanoSIMS offer new possibilities for chemical mapping, high\u2010sensitivity trace element detection, and reduced acquisition times. Variations between individual NM granules can now be investigated effectively and quantitatively by NanoSIMS mapping Cu and Fe. This should yield new insight into the changes in chemical composition of NM pigments during healthy aging and disease.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<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\/jnc13648-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nNeuromelanin\u2010containing organelles of dopamine neurons in normal human substantia nigra were investigated by analytical electron mircoscopy and secondary ion mass spectroscopy (NanoSIMS) yielding the ultrastructure and elemental composition. In neuromelanin granules a significant amount of S, Fe and Cu was found. In lipid bodies an amount of P consistent with the presence of phospholipids was measured. The improved sensitivity of NanoSIMS shows differences in chemical composition between individual neuromelanin granules and allows to study chemical changes of neuromelanin organelles during aging and disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13648","type":"journal-article","created":{"date-parts":[[2016,4,28]],"date-time":"2016-04-28T01:32:53Z","timestamp":1461807173000},"page":"339-353","source":"Crossref","is-referenced-by-count":68,"title":["Elemental mapping of Neuromelanin organelles of human Substantia Nigra: correlative ultrastructural and chemical analysis by analytical transmission electron microscopy and nano\u2010secondary ion mass spectrometry"],"prefix":"10.1111","volume":"138","author":[{"given":"Antje","family":"Biesemeier","sequence":"first","affiliation":[{"name":"Section\u00a0for Experimental Virtreoretinal Surgery Center for Ophthalmology University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Eibl","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhana","family":"Eswara","sequence":"additional","affiliation":[{"name":"Advanced Instrumentation for Ion Nano\u2010Analytics (AINA) Materials Research and Technology Department Luxembourg Institute of Science and Technology (LIST) Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Nicolas","family":"Audinot","sequence":"additional","affiliation":[{"name":"Advanced Instrumentation for Ion Nano\u2010Analytics (AINA) Materials Research and Technology Department Luxembourg Institute of Science and Technology (LIST) Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Wirtz","sequence":"additional","affiliation":[{"name":"Advanced Instrumentation for Ion Nano\u2010Analytics (AINA) Materials Research and Technology Department Luxembourg Institute of Science and Technology (LIST) Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Pezzoli","sequence":"additional","affiliation":[{"name":"Parkinson Institute Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio A.","family":"Zucca","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Technologies National Research Council of Italy Segrate Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Zecca","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Technologies National Research Council of Italy Segrate Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Schraermeyer","sequence":"additional","affiliation":[{"name":"Section\u00a0for Experimental Virtreoretinal Surgery Center for Ophthalmology University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/sia.3550"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.04.004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2011.01.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.05.019"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac801817k"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00138"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604010103"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4633"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490270421"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(95)00206-H"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91361-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1989.tb07264.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-005-0446-6"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01485901"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2005.08.006"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048490"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01923.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91334-B"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1991.tb08170.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-908X.2013.00239.x"},{"key":"e_1_2_8_22_1","unstructured":"INCA(2001)The microanalysis Suite Issue 18b. 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