Metabolomics analysis and biomarker identification for brains of rats exposed subchronically to the mixtures of low-dose cadmium and chlorpyrifos.

Cadmium (Cd) and chlorpyrifos (CPF) are widespread harmful environmental pollutants with neurotoxicity to mammals. Although the exposure to Cd and CPF at the same time may pose a significant risk to human health, the subchronic combined neurotoxicity of these two chemicals at low levels in the brain is poorly understood. In this study, we treated rats with three doses (low, middle, and high) of Cd, CPF, or their mixture for 90 days. No obvious symptom was observed in the treated animals except those treated with high-dose CPF. Histological results showed that middle and high doses of the chemicals caused neuronal cell damage in brains. GC-MS-based metabonomics analysis revealed that energy and amino acid metabolism were disturbed in the brains of rats exposed to the two chemicals and their combinations even at low doses. We further identified the unique brain metabolite biomarkers for rats treated with Cd, CPF, or both. Two amino acids, tyrosine and l-leucine, were identified as the biomarkers for Cd and CPF treatment, respectively. In addition, a set of five unique biomarkers (1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2-ketoisovaleric acid) was identified for the mixtures of Cd and CPF. Therefore, the metabolomics analysis is more sensitive than regular clinical observation and pathological examination for detecting the neurotoxicity of the individual and combined Cd and CPF at low levels. Overall, these results identified the unique biomarkers for Cd and CPF exposure, which provide new insights into the mechanism of their joint toxicity.

[Effect of electroacupuncture on the expression of corticotropin releasing hormone (CRH) and CRHR 1 mRNA in paraventricular nucleus of hypothalamus in stress-induced anxiety rats].

OBJECTIVE: To investigate the effects of electroacupuncture (EA) on the expression of corticotropin releasing hormone (CRH) and CRHR 1 mRNA in paraventricular nucleus (PVN) of hypothalamus, to explore its mechanism in anti-anxiety. METHODS: Thirty-three male SD rats were randomly divided into control, model and EA groups. Chronic emotional stress anxiety model was established by using chronic unpredictable emotional stress stimulation for 21 days. EA (15/25 Hz, 1-2 mA) was applied to "Baihui" (GV 20) and "Sanyinjiao" (SP 6) for 15 min/d and 21 days. The expression of CRH and CRHR 1 mRNA in hypothalamic PVN was measured by immunohistochemistry and in situ hybridization techniques separately. RESULTS: Compared with control group, the values of open-arms entries (OE%) and open-arms time (OT%) in model group were decreased significantly (P<0.01). In comparison with model group, OE% and OT% in EA group were increased obviously (P<0.05, P<0.01). Compared with control group, the optical density values of CRH immuno-reaction positive products and CRHR 1 mRNA expressed neurons of hypothalamic PVN in model group were increased obviously (P<0.05, P<0.01); while in comparison with model group, those of CRH and CRHR 1 mRNA in EA group were significantly decreased (P<0.05, P<0.01). CONCLUSION: EA can effectively relieve chronic stress stimulation induced anxiety in the rat, which is closely related to its effect in down regulating both CRH and CRHR 1 mRNA expression in PVN of hypothalamus.