Effect of trehalose on manganese-induced mitochondrial dysfunction and neuronal cell damage in mice

Chronic overexposure to manganese (Mn) has been verified to induce mitochondrial dysfunction, which is related to oxidative damage. The autophagic-lysosomal degradation pathway plays a vital role in the removal of impaired mitochondria through a specific quality control mechanism termed mitophagy. However, trehalose functions as an inducer of autophagy by an mTOR-independent mechanism, and little data report its effect on Mn-induced mitochondrial dysfunction. To explore the possibility that trehalose could be effective in interfering with the Mn-induced mitochondrial dysfunction, we used trehalose (2% and 4% (g/vol (mL))) in a mouse model of manganism. Our data showed that mice developed weary motor and behavioural deficits after exposure to Mn for 6 weeks. Overexposure to Mn resulted in mitochondrial dysfunction and neuronal cell damage in the basal nuclei of mice, which could be ameliorated by trehalose pre-treatment. Moreover, our results indicated that trehalose pre-treatment significantly reduced the oxidative damage and enhanced the activation of mitophagy. The findings clearly demonstrated that trehalose could relieve Mn-induced mitochondrial and neuronal cell damage through its antioxidative and mitophagy-inducing effects.