Investigating the Neurotoxic Impacts of Arsenic and the Neuroprotective Effects of Dictyophora Polysaccharide Using SWATH-MS-Based Proteomics

Abstract

Arsenic (As) is one of the most important toxic elements in the natural environment. Currently, although the assessment of the potential health risks of chronic arsenic poisoning has received great attention, the research on the effects of arsenic on the brain is still limited. It has been reported that dictyophora polysaccharide (DIP), a common bioactive natural compound found in dietary plants, could reduce arsenic toxicity. Following behavioral research, comparative proteomics was performed to explore the molecular mechanism of arsenic toxicity to the hippocampi of SD (Sprague Dawley) rats and the protective effect of DIP. The results showed that exposure to arsenic impaired the spatial learning and memory ability of SD rats, while DIP treatment improved both the arsenic-exposed rats. Proteomic analysis showed that arsenic exposure dysregulated the expression of energy metabolism, apoptosis, synapse, neuron, and mitochondria related proteins in the hippocampi of arsenic-exposed rats. However, DIP treatment reversed or restored the expression levels of these proteins, thereby improving the spatial learning and memory ability of arsenic-exposed rats. This study is the first to use high-throughput proteomics to reveal the mechanism of arsenic neurotoxicity in rats as well as the protective mechanism of DIP against arsenic neurotoxicity.

Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity

“…40 Compared with these studies, the present study identified changes in the proteins of complex I in the rat cortex following As exposure and clarified the specific dysregulated protein subunits. In contrast, in our previous study, 26 after As treatment, although mitochondrial-related proteins have changed in the hippocampus of rats, they are not proteins of mitochondrial complexes. This clearly requires further study.…”

“…60 Similarly, in our previous study, changes in apoptosis-related proteins were observed in the hippocampus of NaAsO 2 -exposed rats. 26 Therefore, NaAsO 2 -induced apoptosis in the brain cells may be related to its neurotoxicity.…”

“…Studies have found that some edible plants contain biologically active natural compounds that can ameliorate As-induced toxicity. − Dictyophora is a medicinal and edible fungus. Studies have shown that Dictyophora polysaccharides (DIP) extracted from Dictyophora have been shown to have beneficial effects on oxidation, inflammation, and neurodegeneration, , as well as ameliorating As-induced neurotoxicity. , …”

“…28,29 In our previous study, DIP treatment improved spatial learning and memory in As-exposed Sprague-Dawley (SD) rats. 26 Based on the SWATH (sequential windowed acquisition of all theoretical fragment ion) mass spectrometry technique, we investigated the mechanisms of As-induced hippocampal neurotoxicity and neuroprotection by DIP treatment in rats. DIP treatment reversed and restored As-induced energy metabolism, apoptosis, synaptic, neuronal, and mitochondrial-related protein expression in the hippocampus of rats.…”

“…Studies have shown that Dictyophora polysaccharides (DIP) extracted from Dictyophora have been shown to have beneficial effects on oxidation, inflammation, and neurodegeneration, 24,25 as well as ameliorating As-induced neurotoxicity. 26,27 Mass spectrometry (MS) technology has gained rapid development and high innovation in recent years, making it possible to combine proteomics with life science. 28,29 In our previous study, DIP treatment improved spatial learning and memory in As-exposed Sprague-Dawley (SD) rats.…”