Fig. 8

During DA neurodegeneration microglial CX3CR1 protects against neurotoxic CCL2 over-induction by astrocytes. Quantification of the effect of CCL2 deletion on the known increased MPTP-mediated neuronal loss in CX3CR1 deleted mice. Loss of DA neurons was assessed by counting of TH positive DA neurons within the affected SNpc, 7 days after MPTP intoxication. Counts represent the estimated total cells in the entire SNpc (individual mice are shown; red bars, mean; quantification, ANOVA with Holm-Sidak test). Compared to wild-type mice (n = 15; 26% loss of DA neurons, compared to saline- (n = 3) injected controls; **P < 0.01), CX3CR1 deleted mice (CX3CR1^−/−) show increased loss (**P < 0.01) of DA neurons (n = 13; 46% loss of DA neurons, compared to saline (n = 4) injected controls; ***P < 0.001), while the loss of DA neurons in CCL2 deleted mice (CCL2^−/−) (n = 17; 30% loss of DA neurons, compared to saline- (n = 3) injected controls; **P < 0.01), is not different (P > 0.05) from wild-type mice. However, mice with CX3CR1^−/−/CCL2^−/− double deletions (n = 14; 30% loss of DA neurons, compared to saline (n = 3) injected controls; ***P < 0.001) show less MPTP-induced loss of DA neurons than mice deleted for only CX3CR1 (30% compared to 46% loss of DA neurons; **P < 0.01), resetting the increased level of DA neuronal loss observed in CX3CR1^−/− mice (46% loss) to levels observed in normal wild-type mice (26% loss)