Fig. 8

The progression of the motor phenotype and the underlying pathogenic events in the PLP-α-syn transgenic mouse. A robust motor phenotype in the PLP-α-syn (upper panel) is measured at 12 months when the symptomatic motor phase starts. As evident from the brain analysis the neurodegenerative process starts much earlier than the symptomatic presentation of the motor syndrome. The total level of α-syn in the brain of the PLP-α-syn mice remains stable over time, however at 6 months of age soluble oligomeric α-syn species are formed (#). Approximately at the same time strong microglial activation is detected in the substantia nigra (middle panel) that is followed by loss of dopaminergic neurons. The dopaminergic degeneration progresses further and leads to loss of dopaminergic terminals in the striatum as well as loss of striatal GABAergic medium spiny neurons (lower panel) at the time of onset of the motor symptoms. Data are presented as percentage of control wild-type 2 months old mice. Asterisk (*) indicates the time points when significant differences between age-matched wild-type and PLP-α-syn mice occur as presented in detail in the study