{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:04:06Z","timestamp":1779116646743,"version":"3.51.4"},"reference-count":67,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T00:00:00Z","timestamp":1248739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Efficient protection of dopaminergic neurons against a subsequent 6\u2010hydroxydopamine lesion by glial cell line\u2010derived neurotrophic factor (GDNF) gene delivery has been demonstrated. By contrast, the neurorestorative effects of GDNF administered several weeks after the toxin have been less characterized. In particular, whether these were permanent or dependent on the continuous presence of GDNF remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A tetracycline\u2010inducible adeno\u2010associated virus (AAV)\u20101 vector expressing human GDNF cDNA was administered unilaterally in the rat striatum 5 weeks after 6\u2010hydroxydopamine. Rats were treated with doxycycline (dox) or untreated from the day of vector injection until sacrifice (4 or 14 weeks). A sub\u2010group was dox\u2010treated for 7 weeks then untreated until 14 weeks. The motor behavior was assessed by amphetamine\u2010induced rotations and spontaneous forelimb asymmetry. The amounts of tyrosine hydroxylase (TH), serine\u201040\u2010phosphorylated TH (S40\u2010TH) and aromatic amino acid decarboxylase (AADC) proteins were compared by western blotting and the dopamine levels quantified by high\u2010performance liquid chromatography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dox\u2010dependent behavioral improvements were demonstrated 4 weeks post\u2010vector injection. At later time points, spontaneous partial recovery was observed in all rats, but no further improvement was found in dox\u2010treated animals. TH levels were significantly increased in dox\u2010treated rats at all time points. By contrast, striatal dopamine and S40\u2010TH were increased at 4 weeks, but not 14 weeks, and AADC remained unchanged. Dox withdrawal after 7 weeks, resulted in TH levels comparable to the controls at 14 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Delayed GDNF gene delivery only transiently improved dopaminergic function. Over the long term, TH was more abundant, but not functional, and the increase was lost when GDNF gene expression was switched off. Copyright \u00a9 2009 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1377","type":"journal-article","created":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T13:12:55Z","timestamp":1248786775000},"page":"899-912","source":"Crossref","is-referenced-by-count":33,"title":["Reversible neurochemical changes mediated by delayed intrastriatal glial cell line\u2010derived neurotrophic factor gene delivery in a partial Parkinson's disease rat 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