{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:22:48Z","timestamp":1790202168678,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T00:00:00Z","timestamp":1637452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201606170111"],"award-info":[{"award-number":["201606170111"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Misfolded \u03b1\u2010synuclein spreads along anatomically connected areas through the brain, prompting progressive neurodegeneration of the nigrostriatal pathway in Parkinson's disease. To investigate the impact of early stage seeding and spreading of misfolded \u03b1\u2010synuclein along with the nigrostriatal pathway, we studied the pathophysiologic effect induced by a single acute \u03b1\u2010synuclein preformed fibrils (PFFs) inoculation into the midbrain. Further, to model the progressive vulnerability that characterizes the dopamine (DA) neuron life span, we used two cohorts of mice with different ages: 2\u2010month\u2010old (young) and 5\u2010month\u2010old (adult) mice. Two months after \u03b1\u2010synuclein PFFs injection, we found that striatal DA release decreased exclusively in adult mice. Adult DA neurons showed an increased level of pathology spreading along with the nigrostriatal pathway accompanied with a lower volume of \u03b1\u2010synuclein deposition in the midbrain, impaired neurotransmission, rigid DA terminal composition, and less microglial reactivity compared with young neurons. Notably, preserved DA release and increased microglial coverage in the PFFs\u2010seeded hemisphere coexist with decreased large\u2010sized terminal density in young DA neurons. This suggests the presence of a targeted pruning mechanism that limits the detrimental effect of \u03b1\u2010synuclein early spreading. This study suggests that the impact of the pathophysiology caused by misfolded \u03b1\u2010synuclein spreading along the nigrostriatal pathway depends on the age of the DA network, reducing striatal DA release specifically in adult mice.<\/jats:p>","DOI":"10.1111\/bpa.13036","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T23:23:05Z","timestamp":1637536985000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Impact of \u03b1\u2010synuclein spreading on the nigrostriatal dopaminergic pathway depends on the onset of the pathology"],"prefix":"10.1111","volume":"32","author":[{"given":"Fanfan","family":"Sun","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Munich Germany"},{"name":"Center for Neuropathology and Prion Research Ludwig\u2010Maximilians University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando G.","family":"Salinas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Neuroscience Louisiana State University Health Sciences Center \u2013 Shreveport  Shreveport Louisina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severin","family":"Filser","sequence":"additional","affiliation":[{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"},{"name":"Institute for Stroke and Dementia Research Munich University Hospital  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Blumenstock","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Munich Germany"},{"name":"Center for Neuropathology and Prion Research Ludwig\u2010Maximilians University Munich  Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"},{"name":"Molecular Neurodegeneration Research Group Max Planck Institute of Neurobiology  Martinsried Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Medina\u2010Luque","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Munich Germany"},{"name":"Center for Neuropathology and Prion Research Ludwig\u2010Maximilians University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Munich Germany"},{"name":"Center for Neuropathology and Prion Research Ludwig\u2010Maximilians University Munich  Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-369X","authenticated-orcid":false,"given":"Carmelo","family":"Sgobio","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Munich Germany"},{"name":"Center for Neuropathology and Prion Research Ludwig\u2010Maximilians University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00159"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70471-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02010-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227157"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112457"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908005106"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.08.033"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc2487"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-211-45295-0_3"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3039"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02017.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00089"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.20065"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201607305"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709634200"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401076200"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.571"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.05.021"},{"key":"e_1_2_9_20_1","volume-title":"Paxinos and Franklin's the mouse brain in stereotaxic coordinates","author":"Paxinos G","year":"2019"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111749"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05598-1"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.03.001"},{"key":"e_1_2_9_24_1","volume-title":"The mouse brain in stereotaxic coordinates","author":"Franklin KBJ","year":"2001"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.053"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt037"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512876113"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.691592"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.01.064"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.241232"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000243"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902070308"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(80)90198-0"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309143110"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41091-7"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-301817"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000270"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12168"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12565-018-0464-8"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(06)60009-5"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.09.004"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704698114"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.089"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.14802\/jmd.20029"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-019-0917-z"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25135"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4029-08.2009"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00455-7"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.02.004"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4252"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-12-03915.1987"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72176"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00152"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00660.x"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2013.05.006"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.03.022"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2012.01306.x"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12312"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.13036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bpa.13036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.13036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T18:28:43Z","timestamp":1692383323000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.13036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,21]]},"references-count":61,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/bpa.13036"],"URL":"https:\/\/doi.org\/10.1111\/bpa.13036","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,21]]},"assertion":[{"value":"2021-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13036"}}