Proteomic Analysis of Cerebellum in Common Marmoset Exposed to Methylmercury

Abstract

The cerebellum is known as the major target regions of methylmercury (MeHg) toxicity, but the mechanisms are still not fully understood. We studied the effects of MeHg exposure in the cerebellum of common marmoset (Callithrix jacchus) using a shotgun proteomic approach with liquid chromatography coupled to mass spectrometry. A total of 1000 common proteins were identified in all samples, and 102 proteins were significantly differentially expressed in the cerebellum of common marmoset with orally dosed MeHg (1.5 mg MeHg/kg body weight for 2 weeks) compared with those of the control group. Functional enrichment analysis and pathway predictions showed that the differentially expressed proteins were involved in carbohydrate derivative metabolic process, ion transport including synaptic transmission, cell development, and calcium signaling pathway. Cellular component enrichment analysis showed that they were mainly distributed in plasma membrane, excitatory synapse, and synaptic membrane. These results indicate that synaptic transmission and calcium signaling pathways are the core functions affected by MeHg. We found a total of 21 novel proteins affected by MeHg in synaptic transmission and calcium signaling pathways. DLG4: (PSD95) and MIR-19A/MIR-19B were found to be potential key targets leading to the multiple effects of MeHg neurotoxicity. These results show the global effects of MeHg on cellular functions and pathways leading to neurological deficits in common marmoset.

Keywords: calcium signaling pathway; methylmercury; neurotoxicity; primate; proteomics; synaptic transmission.