Atmospheric PM_2.5 aspiration causes tauopathy by disturbing the insulin signaling pathway

Epidemiological and toxicological studies have shown that ambient fine particulate matter (PM_2.5) is a healthy risk factor for neurodegenerative diseases. Hyperphosphorylated tau is the common feature of numerous neurodegenerative diseases known as tauopathy, which could be inhibited by insulin stimulation. However, the effects of PM_2.5 on tau protein injury by disturbing the insulin signaling pathway still need to be illuminated. In present study, male C57BL/6 J mice were administered with PM_2.5 to determine whether PM_2.5 inhalation can induce tauopathy via the insulin resistance (IR) related pathway (IRS-1/AKT/GSK-3β signaling pathway). The results showed that PM_2.5 treatment induced the generation of phosphorylated tau (P-tau) and contributed to the development of tauopathy because of the insulin signaling disorders in insulin targeting organs. As expected, the occurrence of central and peripheral IR and accompanying hyperinsulinemia aggravated the disturbance of the IRS-1/AKT/GSK-3β signaling pathway. These observations indicated that PM_2.5 exposure led to neurodegenerative tau lesion, and insulin signaling pathway might be a potential therapeutic target for tauopathy.