{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:31:53Z","timestamp":1773268313916,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T00:00:00Z","timestamp":1080259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2004,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Administration of the neurotoxicant 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) to C57BL\/6 mice targets nigrostriatal dopaminergic neurons, leading to cell death and the depletion of striatal dopamine. After MPTP lesioning in young adult mice, surviving nigrostriatal dopaminergic neurons display robust and reproducible return of striatal dopamine weeks to months after injury. Thus, the mouse provides an excellent model with which to investigate the mechanisms underlying neuroplasticity of the nigrostriatal system following neurotoxic injury. The purpose of this study was to analyze proteins and mRNA transcripts of genes involved in dopamine biosynthesis (tyrosine hydroxylase; TH) and uptake (dopamine transporter; DAT) with regard to time course (7\u201390 days) after MPTP lesioning. Molecular analysis using immunohistochemistry and Western immunoblotting techniques demonstrated an increase in striatal TH by 30\u201360 days postlesioning that returned to near\u2010control (prelesioned) levels by 60\u201390 days. In situ hybridization histochemistry indicated that this increase in TH protein might be due in part to increased TH mRNA expression in surviving nigrostriatal dopaminergic neurons. Analysis of TH protein at 7, 30, 60, and 90 days postlesioning with two\u2010dimensional polyacrylamide gel electrophoresis in conjunction with Western immunoblotting revealed altered TH protein isoforms migrating at isoelectric points different from those of the native isoform. In contrast to TH protein, which returned to prelesioned levels by 60 days, DAT protein analysis showed that increased expression of striatal DAT protein did not return to near\u2010prelesion levels until 90 days postlesioning. These results suggest that TH and DAT may differ in their time course of expression in surviving dopaminergic neurons and may play a role in mediating the return of striatal dopamine. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.20114","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T22:01:56Z","timestamp":1080338516000},"page":"539-550","source":"Crossref","is-referenced-by-count":73,"title":["Tyrosine hydroxylase and dopamine transporter expression following 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010induced neurodegeneration of the mouse nigrostriatal pathway"],"prefix":"10.1002","volume":"76","author":[{"given":"Michael W.","family":"Jakowec","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Nixon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Hogg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"McNeill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle M.","family":"Petzinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,3,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1523\/JNEUROSCI.01-05-00493.1981","article-title":"Short and long term changes in tyrosine hydroxylase activity in rat brain after subtotal destruction of central noradrenergic neurons","volume":"1","author":"Acheson AL","year":"1981","journal-title":"J Neurosci"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10196"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7659"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-17-06761.1997"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(20001201)38:3<363::AID-SYN16>3.0.CO;2-A"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64041669.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01391-1"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"10489","DOI":"10.1016\/S0021-9258(18)67410-1","article-title":"Identification of four phosphorylation sites in the N\u2010terminal region of tyrosine hydroxylase","volume":"261","author":"Campbell DG","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902620110"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01491-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00009-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.355"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.2.617"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1987.tb02837.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1988.tb03063.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1093\/clinchem\/30.12.1933","article-title":"Two\u2010dimensional electrophoresis and \u201cultrasensitive\u201d silver staining of cerebrospinal fluid proteins in neurological diseases","volume":"30","author":"Harrington MG","year":"1984","journal-title":"Clin Chem"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1016\/S0021-9258(19)67644-1","article-title":"Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. 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