Involvement of sirtuins (Sirt1 and Sirt3) and aryl hydrocarbon receptor (AhR) in the effects of triclosan (TCS) on production of neurosteroids in primary mouse cortical neurons cultures.

Epidemiological studies have shown the presence of triclosan (TCS) in the brain due to its widespread use as an antibacterial ingredient. One of the confirmed mechanisms of its action is the interaction with the aryl hydrocarbon receptor (AhR). In nerve cells, sirtuins (Sirt1 and Sirt3) act as cellular sensors detecting energy availability and modulate metabolic processes. Moreover, it has been found that Sirt1 inhibits the activation of estrogen receptors, regulates the androgen receptor, and may interact with the AhR receptor. It is also known that Sirt3 stimulates the production of estradiol (E2) via the estradiol receptor ß (Erß). Therefore, the aim of the present study was to evaluate the effect of TCS alone or in combination with synthetic flavonoids on the production of neurosteroids such as progesterone (P4), testosterone (T), and E2 in primary neural cortical neurons in vitro. The contribution of Sirt1 and Sirt3 as well as AhR to these TCS-induced effects was investigated as well. The results of the experiments showed that both short and long exposure of neurons to TCS increased the expression of the Sirt1 and Sirt3 proteins in response to AhR stimulation. After an initial increase in the production of all tested neurosteroids, TCS acting for a longer time lowered their levels in the cells. This suggests that TCS activating AhR as well as Sirt1 and Sirt3 in short time intervals stimulates the levels of P4, T, and E2 in neurons, and then the amount of neurosteroids decreases despite the activation of AhR and the increase in the expression of the Sirt1 and Sirt3 proteins. The use of both the AhR agonist and antagonist prevented changes in the expression of Sirt1, Sirt3, and AhR and the production of P4, T, and E2, which confirmed that this receptor is a key in the mechanism of the TCS action.