%A Penttinen,Anna-Maija %A Parkkinen,Ilmari %A Voutilainen,Merja H. %A Koskela,Maryna %A Bäck,Susanne %A Their,Anna %A Richie,Christopher T. %A Domanskyi,Andrii %A Harvey,Brandon K. %A Tuominen,Raimo K. %A Nevalaita,Liina %A Saarma,Mart %A Airavaara,Mikko %D 2018 %J Frontiers in Neurology %C %F %G English %K neurotrophic factors,neurodegeneration,gdnf,splice variant,Alternative Splicing,tyrosine hydroxylase,Dopamine %Q %R 10.3389/fneur.2018.00457 %W %L %M %P %7 %8 2018-June-20 %9 Original Research %# %! Neuroprotective effects of β-GDNF %* %< %T Pre-α-pro-GDNF and Pre-β-pro-GDNF Isoforms Are Neuroprotective in the 6-hydroxydopamine Rat Model of Parkinson's Disease %U https://www.frontiersin.org/articles/10.3389/fneur.2018.00457 %V 9 %0 JOURNAL ARTICLE %@ 1664-2295 %X Glial cell line-derived neurotrophic factor (GDNF) is one of the most studied neurotrophic factors. GDNF has two splice isoforms, full-length pre-α-pro-GDNF (α-GDNF) and pre-β-pro-GDNF (β-GDNF), which has a 26 amino acid deletion in the pro-region. Thus far, studies have focused solely on the α-GDNF isoform, and nothing is known about the in vivo effects of the shorter β-GDNF variant. Here we compare for the first time the effects of overexpressed α-GDNF and β-GDNF in non-lesioned rat striatum and the partial 6-hydroxydopamine lesion model of Parkinson's disease. GDNF isoforms were overexpressed with their native pre-pro-sequences in the striatum using an adeno-associated virus (AAV) vector, and the effects on motor performance and dopaminergic phenotype of the nigrostriatal pathway were assessed. In the non-lesioned striatum, both isoforms increased the density of dopamine transporter-positive fibers at 3 weeks after viral vector delivery. Although both isoforms increased the activity of the animals in cylinder assay, only α-GDNF enhanced the use of contralateral paw. Four weeks later, the striatal tyrosine hydroxylase (TH)-immunoreactivity was decreased in both α-GDNF and β-GDNF treated animals. In the neuroprotection assay, both GDNF splice isoforms increased the number of TH-immunoreactive cells in the substantia nigra but did not promote behavioral recovery based on amphetamine-induced rotation or cylinder assays. Thus, the shorter GDNF isoform, β-GDNF, and the full-length α-isoform have comparable neuroprotective efficacy on dopamine neurons of the nigrostriatal circuitry.