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).