Abstract: Objective To develop an animal model illustrating the effects of carbon disulfide exposure on learning ability, to detect the pathological changes of the hippocampus caused by carbon disulfide exposure, and to reveal its underlying mechanisms. Methods A total of 80 Wistar rats were randomly divided into 4 groups: control, low, medium and high dose groups, followed with the treatment of corn oil, 200, 400 and 600 mg/kg of carbon disulfide, respectively, by gavage daily for 20 days. The learning ability of the rats was tested from day 16 to 20 with Morris Water Maze. The pathological changes of the hippocampus was detected with Nissl staining and immunohistochemical staining. The level of nitric oxide (NO) and activity of nitric oxide synthase (NOS) were measured with biochemical assay kits. Results The swimming distance and escape latency of the carbon disulfide-treated rats increased (P<0.05) compared to those of the control group, in a dose-dependent manner. The neurons in the CA3 and DG area of hippocampus were found with increased size, lighter color, and disordered cell arrangement in Nissl staining. The neural nuclei (NeuN) staining showed a significant loss of neurons in CA3 region of the 600 mg/kg carbon disulfide treated animals compared to the control group (P<0.01). The further detection on the level of NO and activity of NOS in the hippocampus showed an increase in the medium and high dose group rats. Conclusion Exposure to carbon disulfide could cause neuronal loss in the hippocampus CA3 region, resulting in learning incapability of the exposed animals. The underlying mechanisms of the neuronal damage might be attributed to NO and NOS change in the hippocampus.

Key words: Carbon disulfide, Hippocampus, Nitric oxide, Learning ability