{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:27:06Z","timestamp":1790422026195,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":2625,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1997,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glial cell line\u2013derived neurotrophic factor (GDNF) stimulates the nigrostriatal dopaminergic pathway and improves motor functions in animal models of parkinsonism. Sinemet is currently the most widely used drug for treating Parkinson's disease. The present study has evaluated GDNF\u2013Sinement interactions in parkinsonian rhesus monkeys. Both GDNF and Sinemet, when given alone, significantly improved total parkinsonian scores. The response to Sinement did not change after intracerebroventricular vehicle injections. In contrast, there was a functional interaction between GDNF and levodopa. When comparing the levodopa dose response before and after GDNF treatment, significant behavioral improvements were seen after trophic factor administration at every levodopa dose level except 500 mg. Adverse responses to Sinemet treatment alone in parkinsonian animals included vomiting, dykinesias, dystonias, and stereotypic movements. Combined GDNF\u2013Sinemet treatment significantly reduced the occurrence of these levodopa\u2010induced side effects, with a &gt;90% decrease in adverse responses seen at the mid\u2010Sinemet (250 mg levodopa\u201325 mg carbidopa) dose level. The only side effect from GDNF treatment was a transitory weight loss. Thus, combined GDNF\u2013Sinemet treatment could be of therapeutic value in treating parkinsonism, by producing a greater functional response and by mitigating adverse responses to Sinemet treatment.<\/jats:p>","DOI":"10.1002\/ana.410420212","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:04:12Z","timestamp":1104591852000},"page":"208-214","source":"Crossref","is-referenced-by-count":53,"title":["Glial cell line\u2013derived neurotrophic factor\u2013levodopa interactions and reduction of side effects in parkinsonian monkeys"],"prefix":"10.1002","volume":"42","author":[{"given":"Yasuyuki","family":"Miyoshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliza","family":"Ovadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Lapchak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Hilt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Lebel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kryscio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don M.","family":"Gash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"19","article-title":"Biochemical pathophysiology of Parkinson's disease","volume":"45","author":"Hornykiewicz O","year":"1986","journal-title":"Adv Neurol"},{"key":"e_1_2_1_3_2","first-page":"1","article-title":"Overview of morphological changes in Parkinson's disease","volume":"45","author":"Jellinger K.","year":"1986","journal-title":"Adv Neurol"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.139.4.494"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.9_Part_1.1253"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)91146-1"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1518"},{"issue":"6","key":"e_1_2_1_8_2","first-page":"47","article-title":"Neuropsychological and psychiatric side effects in the treatment of Parkinson's disease","volume":"43","author":"Saint\u2010Cyr JA","year":"1993","journal-title":"Neurology"},{"key":"e_1_2_1_9_2","first-page":"242","article-title":"Degeneration of dopaminergic neurons and free radicals; 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