Effect of SA on MPTP-induced neurotoxicity in C57BL/6 mice
We also determined the effect of SA on the MPTP-induced PD mouse model.
First, motor dysfunction was tested using the rotarod test and pole
test. In the rotarod test, the latency to fall was markedly decreased in
the MPTP group (51.7\(\pm\)11.3 s) compared with the control group
(123.8\(\pm\)14.3 s). After 10 and 20 mg/kg SA treatment, the latency to
fall was increased 2.2- and 2.3-fold compared with MPTP alone,
respectively (Figure 3A). The MPTP treatment group also impaired
performance (12.2 \(\pm\) 1.4 s) compared with the control group (7.5\(\pm\) 0.3 s) in the pole test. However, 10 and 20 mg/kg SA treatment
improved the performance to approximately 86 and 72%, respectively
(Figure 3B). Similar to an in vitro experiment, we detected the
protein expression of TH. Several studies showed that TH levels were
reduced in the SNpc of MPTP-treated mice, recapitulating the main
neuropathological characteristic of PD (Hayashi et al., 2013; Laloux et
al., 2008). In this study, the protein expression of TH in the SNpc was
significantly reduced to 39% in MPTP-treated mice compared with that in
the control group. SA at 20 mg/kg protected the loss of dopaminergic
neurons (Figure 3E). In the mitochondrial function assay using ATP level
and GDH activity, these two factors decreased to 83% and 55% in the
MPTP group compared with the control group, respectively. SA at 20 mg/kg
also improved these changes (Figure 3C and D). The protein expression of
REV-ERB α was also similar to the in vitro experimental results.
The protein expression of REV-ERB α was approximately 64% lower than
that of the control group, while 20 mg/kg SA attenuated this decrease.
(Figure 3F). Consistent with the western blotting results, SA recovered
both the protein expression of REV-ERB α and the loss of dopaminergic
neurons, as shown by immunofluorescent labelling of REV-ERB α and TH
(Figure 3G).