Fig. 5.

Characterization of a rat model of the presymptomatic phase of Parkinson’s disease (PD). In a rat model of PD onset based on the bilateral administration of 6-hydroxydopamine (6-OHDA, 20 μg in each striatum), it is possible to distinguish a presymptomatic phase at 7 days after 6-OHDA exposure and a symptomatic phase at 21 days after exposure. Representative coronal sections of the dorsolateral striatum (A–C; away from the injection site; scale bars: 200 μm) or substantia nigra (F–H; scale bars: 150 μm) stained for the dopaminergic marker, tyrosine hydroxylase (TH), from saline-treated rats and 7 days (B, G) or 21 days (C, H) after the bilateral administration of 6-OHDA (20 μg in each striatum), with the presentation of the immunohistochemical quantification of TH density in the striatum (D) or substantia nigra (I). The average dopamine levels in the striatum (E) and in the mesencephalon (J) confirmed a partial depletion of dopamine in the striatum with no alteration in the mesencephalon at 7 days after 6-OHDA administration, which was aggravated in the striatum and became evident in the mesencephalon at 21 days after 6-OHDA administration. This translated into a non-significant modification of motor performance at 7 days, which evolved into an overt motor dysfunction at 21 days, as heralded by the total distance travelled (K), the number of ambulatory episodes (L), the number of rearing events in an open-field test (M), as well as the number of touches with both paws in the cylinder test (N) and the time before falling in the rotarod test (O). Data are mean ± SEM of 6–8 rats per group; *p < 0.05 vs. control and **p < 0.05 vs. 7 days, using either a one-way ANOVA followed by Bonferroni’s post hoc test