Effect of SA on MPTP-induced neurotoxicity in C57BL/6 mice through inhibition of REV-ERB α
Next, we investigated whether REV-ERB α was directly linked with the protective effect of SA in the MPTP-induced neurotoxicity mouse model. SR8278 (SR), a REV-ERB α antagonist, was employed to inhibit the protein expression of REV-ERB α. In the motor function test, co-treatment with SA and SR markedly decreased motor performance compared with that of the SA treatment group in the rotarod test and pole test (Figure 5A and B). In addition, the protein expression of TH and REV-ERB α in the SNpc was markedly decreased to approximately 70 and 78% in the SA and SR co-treatment group compared with that in the SA group, respectively (Figure 5E and F). The ATP level and GDH activity also decreased to approximately 88% and 83%, respectively, in the SA and SR co-treatment group compared with the SA group (Figure 5C and D). Consistent with the previous data, co-treatment with SA and SR showed an increasing tendency of Drp1 protein expression compared with the SA treatment group (Figure 6A). In addition, phospho-Drp1 Ser616 significantly increased 1.3-fold in both SA and SR-treated mice compared with the SA group, but phospho-Drp1 Ser637 did not change (Figure 6B and C). The ratio of phospho-Drp1 Ser616/637 also increased 1.2-fold in the SA and SR co-treatment group compared with the SA treatment group (Figure 6D).