Resistance to MPTP-Neurotoxicity in α-Synuclein Knockout Mice Is Complemented by Human α-Synuclein and Associated with Increased β-Synuclein and Akt Activation
Figure 2
Effects of sub acute MPTP regimen, aging, and transgene expression level on the MPTP sensitivity of nigral dopaminergic neurons in human A53T α-synuclein transgenic mice.
A. Stereologic cell counts of total and TH-immunopositive neurons of SNpc in non transgenic and human A53T transgenic mice (line N2-5, ∼3-fold) analyzed two weeks after a sub-acute paradigm of MPTP (30 mg MPTP/kg free base once a day for 5 days). Although sub acute MPTP caused significant reductions in total and TH-positive neurons no significant differences were seen among transgenic and non transgenic mice receiving the same treatments (saline or MPTP). B. TH-positive and total neuronal counts in SNpc of 12-14 month old non transgenic and human A53T transgenic mice (line N2-5) after acute MPTP (15 mg MPTP/kg free base X4, every 2 h) at 7 days. Acute MPTP in older mice caused significant reduction in total and TH-positive neurons no significant differences were seen among transgenic and non transgenic mice receiving the same treatments (saline or MPTP). C. Cell counts of TH-positive and total neurons in high expressing lines of human A53T transgenic mice (G2-3 line, ∼6-fold) 7 days after acute MPTP intoxication (18 mg MPTP/kg free base X4, every 2 h). MPTP-intoxication resulted in a significant reduction of total and TH-positive neuronal counts in non transgenic and high expressing lines of A53T transgenic mice compared to saline treatments. A moderate increase in the vulnerability was observed in A53T transgenic mice. Data represent mean ± SEM. *p<0.05, statistical significance versus saline controls using two way ANOVA, n = 5-6 per group, n.s., not significant. #, significant using Neuman-Keuls post-test (p<0.05) but not with the Tukey-Kramer post test.