Lithium inhibits oxidative stress-induced neuronal senescence through miR-34a.

Neuronal senescence, triggered by telomere shortening, oncogene activation, DNA damage, or oxidative stress, has been associated with neurodegenerative diseases' pathogenesis. Therefore, preventing neuronal senescence could be a novel treatment strategy for neurodegenerative diseases. Lithium (Li), the first-line treatment against bipolar disorder, has been shown to have neuroprotective effects in clinical, pre-clinical, and in vitro studies. Li can protect cells from senescence, and its effect on neuronal senescence was investigated in our study. Furthermore, we also investigated the effects of Li on the senescence-associated miR-34a/Sirt1/p53 pathway. In this study, hydrogen peroxide was used as an inducer for the "stress-induced premature senescence" model. In the senescence model, we have assessed Li's effects on senescence by analyzing beta-galactosidase activity, Sudan Black B, and senescence-associated heterochromatin foci (SAHF) stainings, and on cell cycle arrest by BrdU staining. Furthermore, expression levels of senescence and cell cycle arrest-related proteins (p53, p21, p16INK4a, and SIRT1) by western blotting. Finally, the effects of Li on senescence-associated miR-34a levels were measured by quantitative PCR. We show via Sudan Black B staining, beta-Gal activity assay, and by detecting SAHF, Li protects against senescence in neuronal cells. Then, Li's effect on signaling has also been determined on pathways involved in senescence and cell cycle arrest. Moreover, we have observed that Li has a modulatory effect on miR-34a expression. Therefore, we posit that Li suppresses senescence in neuronal cells and that this effect is mediated through miR-34a/Sirt1/p53 axis