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Arsenic exposure-induced cognitive disorders have attracted much attention from scientists. This study employed RNA sequencing to investigate the potential molecular mechanisms underlying neurobehavioral alterations in mice due to arsenic exposure at a transcriptomic level. Male C57BL/6 mice were divided into four groups, the control group (group C), low-dose group (group L), medium-dose group (group M) and high-dose group (group H), which drank deionized water containing 0, 0.15, 1.5 and 15 mg·L-1 AS2O3 respectively for 12 weeks. Cognitive function of the mice was analyzed by the novel object recognition test. RNA sequencing followed by GO enrichment analysis and KEGG pathway enrichment analysis identified differentially expressed genes (DEGs) between control and high dose groups. qRT-PCR was conducted to verify the gene expression levels of target genes. A protein-protein interaction network (PPI) was constructed to identify hub genes from the gene module with the highest connection degree. The findings indicated a significant decrease in both exploration and discrimination indices for arsenic-exposed groups compared to controls. There were 181 DEGs in the high-dose group compared with the control. A total of 217 significantly enriched GO terms were obtained including behavior, regulation of multicellular biological processes, learning and memory, cognition, etc. KEGG enrichment analysis showed that 128 DEGs were enriched in 38 pathways, including cholinergic synapses, dopamine synapses, neurotrophic factor signaling pathways, etc. 7 hub genes were screened from the gene module with the highest connection degree, which were fos, tac1, gad2, drd2, ppp1r1b, chat and drd1a. The results of gene expression levels from qRT-PCR are in good agreement with those from RNA-seq, reflecting the reliability of RNA-seq. It was observed that arsenic exposure led to a significant reduction in mice' s cognitive abilities. The identified hub genes and key pathways from this study offer valuable insights into exploring the mechanisms underlying neurobehavioral changes in mice due to arsenic exposure. [ABSTRACT FROM AUTHOR]

Objective: To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats. Methods: From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl(2)·4H(2)O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl(2)·4H(2)O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results: The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased ( P <0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased ( P <0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day ( P <0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased ( P <0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened ( P <0.05) , and the average number of crossing the original platform was increased ( P <0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups ( P <0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased ( P <0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese ( P <0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group ( P <0.05) . Conclusion: Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.