Abstract:
Salsolinol (SAL), an endogenous neurotoxin has been identified as a potential aetiological factor in Parkinson’s disease (PD). Its neurotoxicity through apoptosis induction and oxidative stress were extensively studied in dopaminergic cell lines, however the influence of SAL on other cell types have yet to be explored. As microglia hold integral role in neuroprotection and maintenance of brain homeostasis, the present study aimed to investigate the apoptotic effects of SAL on microglial cells. The influence of SAL on cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was applied to observe the distribution of cell cycle phases following SAL treatment. Caspase assays were used to detect caspase activities in BV2 cells, whereas the production of reactive oxygen species (ROS) in BV2 cells was measured using 2',7'-dihydrodichlorofluorescein diacetate (DCFH-DA) assay. SAL was demonstrated to exert a dose- and time-dependent cytotoxicity on BV2 cells. Significant increase in subG1 population implicated that the cells were undergoing apoptotic cell death. SAL also induced activation of multiple caspases in BV2 cells, such as caspase-3/7, -8 and -9. Interestingly, ROS assay revealed SAL at lower concentrations significantly reduced intracellular ROS levels, however a sudden surge in ROS production was observed when the cells were exposed to high-dose SAL. These findings suggest that SAL could be neuroprotective at low concentrations, however its accumulation could induce significant apoptotic deaths and oxidative stress. The neurotoxicity of SAL not only affects dopaminergic neurons, but it can also be extended to the microglia population. This provides new insights on the role of microglia in PD pathogenesis.
