The neuroprotective effects of lithium and valproic acid on SH-SY5Y cell line

Nowadays, there is not any definite treatment method for neurodegenerative diseases; however, some approaches may be useful for neuroprotection by application of an agent, which may serve for the reversal of neuronal damage or prevention from further neuronal damage.In this study, it was aimed to analyze whether lithium and valproic acid, which are mood stabilizers, have neuroprotective effects on human neuroblastoma cell line treated with mitochondrial inhibitor paraquat (methylviologen dichloride). Furthermore, the mechanism of protection was further analyzed.In the first part of the study, the procteting effects of 24 hours pre-incubation of 2-10 mM Lithium and 100-1000 ?M valproic acid followed by the damage caused by 500-1000 ?M paraquat was assesed. In the second part of the experiment, it was shown that paraquat causes apoptotic cell death in SH-SY5Y cells. Then, the impact of lithium on Bcl-2, Bax and Bcl-xl, which are responsible for promotion of apoptosis pathway, was analyzed using qPCR.As a result of this study, lithium showed protective effects at doses of 2mM and 5mM in 24 hours pre-incubation. On the other hand, Valproic acid did not show any protecting affects. Furthermore, lithium pre-incubation caused up-regulation of anti-apoptotic Bcl-2 and Bcl-xl mRNAs, while pro-apoptotic Bax was decreased.In this study, the anti-apoptotic effect of lithium on the paraquat-induced neurotoxicity model is shown for the first time.