Activation of lysosomal degradative pathway in spinal cord tissues of carbon disulfide-treated rats

• Carbon disulfide resulted in increased number of lysosomes in rat motor neurons.
• Carbon disulfide increased the level of LC3-II in rat spinal cord.
• Carbon disulfide increased the expression and activity of LAMP-1 and cathepsin B.
• Carbon disulfide activated the autophagy–lysosomal pathway in neurons.

Chronic exposure to carbon disulfide (CS2) can induce polyneuropathy in occupational worker and experimental animals, but underlying mechanism for CS2 neuropathy is currently unknown. In the present study, male Wistar rats were randomly divided into three experimental groups and one control group. The rats in experimental groups were treated with CS2 by gavage at dosages of 200, 400 and 600 mg/kg/day respectively, six times per week for 6 weeks. The formation of autophagosomes and lysosomes in motor neurons of rat spinal cord was observed by transmission electron microscopy, the level of autophagy-related proteins, lysosome-associated membrane protein 1 (LAMP-1), and cathepsin B in spinal cord tissues was determined by Western blot analysis, and the activity of cathepsin B was measured by fluorescence assay. The results demonstrated that the number of lysosomes in motor neurons was markedly increased in CS2-treated rats. In the meantime, the administration of CS2 significantly increased the level of microtubule-associated protein light chain 3-II (LC3-II), Atg1, UVRAG and LAMP-1 in rat spinal cord. Furthermore, the content and activity of cathepsin B in rat spinal cord also showed a significant elevation. Taken together, this study suggested that CS2 intoxication was associated with the activation of lysosomal degradative machinery, which might play a protective role against CS2-induced neuronal damage.