Oxidative stress induced by sustained supraphysiological intrastriatal GDNF delivery is prevented by dose regulation.

"the pac1-v16 plasmid comprising aav itrs bracketing a bidirectional tetracycline-responsive cassette expressing the mutant dox-hypersensitive reverse tetracycline transactivator rttav16 and egfp or human gdnf ( hgdnf ) cdna (genbank: ah003115 2) in the opposite direction have been described previously and were deposited at addgene ( www addgene org ; plasmid no 122035)."

"Declaration of interests The authors declare no competing interests."

"We thank Pascal Steullet (Center for Neuropsychiatric Research, CHUV) as well as Pavlina Konstantinova, Bas Blits, and Harald Petry (UniQure) for helpful discussions. We thank Ali Scherz for technical help and Romain-Daniel Gosselin (Precision Medicine Unit, CHUV) for his help in statistical analyses. We thank Abdelwahed Chtarto (Free University of Brussels) for the gift of the AAV-V16 plasmids, Atze Das (Amsterdam Medical Center) for the gift of the V16 transactivator, and Jolanda Liefhebber (UniQure) for sharing the sequence of GDNF primers for vector titration. Scanning and confocal imaging were performed in CIF Lausanne University imaging platform. We particularly thank Luigi Bozzo and Florence Morgenthaler-Grand. The rats were housed and fed with dox diet when indicated at the Center for the Study of Behavior at the Center for Neuropsychiatric Research, CHUV. This work was supported by a grant from the Swiss National Foundation (10.13039/501100001711SNF grant no. 31003A_179527) to L.T., by EU FP7 Marie Curie IAPP BrainVectors (contract no. 286071) to L.T., by UniQure to L.T. and M.H.-C., and by the “Spanish Ministry of Sciences and Innovation (PID2019-105795RB-I00)” to T.G.-H. The authors declare that there are no additional disclosures to report."