{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:16:09Z","timestamp":1790018169157,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,1,26]],"date-time":"2015-01-26T00:00:00Z","timestamp":1422230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University Clinics Giessen and Marburg"},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["HO2402\/6-2"],"award-info":[{"award-number":["HO2402\/6-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previously, we demonstrated that systemically injected extracellular domain of neuregulin\u20101\u03b21 (Nrg1\u03b21), a nerve growth and differentiation factor, passes the blood\u2010brain barrier and rescues dopaminergic neurons of substantia nigra in the 6\u2010hydroxydopamine\u2010mouse model of Parkinson's disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>). Here, we studied the effects of peripherally administered Nrg1\u03b21 in another toxin\u2010based mouse model of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. For this purpose, (i) nigrostriatal pathway injury was induced by treatment of adult wild\u2010type mice with 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>) in acute and subchronic paradigms; and (ii) Nrg1\u03b21 or saline (control) were administered 1\u00a0h before each <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> injection. We found that Nrg1\u03b21 significantly reduced the loss of nigral dopaminergic neurons in both intoxication paradigms (7\u00a0days post\u2010injection). However, Nrg1\u03b21 did not reverse <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>\u2010induced decrease in dopamine levels and dopaminergic fibers in the striatum. We also show that <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> conversion to its toxic metabolite 1\u2010methyl\u20104\u2010phenylpyridinium as well as levels of dopamine transporter, mediating intracellular uptake of 1\u2010methyl\u20104\u2010phenylpyridinium, are unaffected by Nrg1\u03b21. Finally, neuroprotective properties of Nrg1\u03b21 on nigral dopaminergic neurons are specifically mediated by ErbB4 as revealed through the study of ErbB4 knockout mice. In conclusion, systemically administered Nrg1\u03b21 protects midbrain dopaminergic neurons against this <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010related toxic insult. Thus, Nrg1\u03b21 may have a benefit in the treatment of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients.\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\/jnc13026-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Previously, we demonstrated that systemically administered neuregulin\u20101\u03b21 (Nrg1\u03b21) passes the blood\u2010brain barrier, phosphorylates ErbB4 receptors and elevates dopamine (DA) levels in the nigrostriatal system of healthy mice. Nrg1\u03b21 protects nigral DAergic neurons in the 6\u2010hydroxydopamine (6\u2010OHDA) mouse model of Parkinson's disease (PD). Here, we show that Nrg1\u03b21 rescues nigral DAergic neurons also against 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010induced cell death. ErbB4 expression is essential for the neuroprotective effect of Nrg1\u03b21 on midbrain DAergic neurons. Nrg1\u03b21 might be beneficial in PD treatment.<\/jats:p>","DOI":"10.1111\/jnc.13026","type":"journal-article","created":{"date-parts":[[2015,1,10]],"date-time":"2015-01-10T13:27:37Z","timestamp":1420896457000},"page":"590-597","source":"Crossref","is-referenced-by-count":28,"title":["Systemically administered neuregulin\u20101\u03b21 rescues nigral dopaminergic neurons via the ErbB4 receptor tyrosine kinase in <scp>MPTP<\/scp> mouse models of Parkinson's disease"],"prefix":"10.1111","volume":"133","author":[{"given":"Candan","family":"Depboylu","sequence":"first","affiliation":[{"name":"Department of Neurology Philipps University Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"R\u00f6sler","sequence":"additional","affiliation":[{"name":"Department of Neurology Philipps University Marburg Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Department of Neurology Philipps University Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang H.","family":"Oertel","sequence":"additional","affiliation":[{"name":"Department of Neurology Philipps University Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"Department of Neurology Philipps University Marburg Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Germany"},{"name":"Department of Neurology Technical University Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.03.022"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302679"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.10.035"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00210-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07284.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.05.006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.10.050"},{"key":"e_1_2_8_11_1","volume-title":"The Mouse Brain in Stereotactic Coordinates","author":"Franklin K. 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