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

Abstract

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 6weeks. 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.