Figure 1.
AAV mediated A53T α-synuclein overexpression. A–E, At 4 weeks after AAV injection, human α-synuclein expression was detected in the SN area and was colocalized with TH-positive neurons. F, Human α-synuclein was highly expressed in the dorsolateral striatum where transduced DA neurons project their synaptic terminals. G, H, Many α-synuclein overexpressing axons showed swollen and bulging morphology compared with GFP expressing axons in the control striatum starting at 4 weeks and maintained till later stages (supplemental Fig. 1D, available at www.jneurosci.org as supplemental material). I, J, A53T α-synuclein overexpression resulted in a loss of TH-positive cells at 17 (32 ± 8%) and 24 (56.3 ± 3%) weeks compared with GFP overexpression. K, L, HPLC analysis in the striatal tissue demonstrated DOPAC content was significantly increased in the A53T α-synuclein overexpressing striatum at 4, 8, and 17 weeks (L) without changing dopamine (DA) content at these times (K). Striatal DA content was reduced only at 24 weeks after A53T α-synuclein overexpression (K). M, DOPAC/DA ratios were increased in A53T α-synuclein overexpressing striatum at 8, 17, and 24 weeks. Data are shown as means ± SEM (AAV GFP, n = 10∼12; AAV α-synuclein, n = 12∼15; *p < 0.05; **p < 0.01 two-tail t test).