Expression Chang Of 5-HT And BDNF In Rats Of Chronic Manganism

Objective:To observe depression behavior and the expression changes of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) in rats with chronic manganism.Methods:eighty male Sprague—Dawley rats were randomly divided into control group (n=20) and experimental group (n=60). The experimental group was divided into three subgroups:low-dose group (n=20), middle-dose group (n=20), high-dose group (n=20). The rats in control group were given intraperitoneal injection of normal saline while the rats in low-dose group, middle-dose group, high-dose group were given intraperitoneal injection of 5 mg/kg,15 mg/kg and 25 mg/kg manganese chloride tetrahydrate, respectively for 5 days once a week and lasting for 12 weeks. The depressive behavior changes of rats were observed by sucrose preference test and open field test. The content of manganese in the striatum is detected by Inductively Coupled Plasma- Atomic Emission Spectrometry (ICP-AES). The expression of 5-HT in frontal cortex and hippocampus of rats were determined by high performance liquid chromatography (HPLC) and BDNF of rats were obsersed by Western blot. The expression of BDNFmRNA and tryptophan hydroxylase 2(TPH2 is the rate-limiting enzyme for the synthesis of 5-HT)was detected using real-time fluoescence quantitative PCR.Result:The chronic manganese poisoning rats could performance depression-like behavior from results of sucrose consumption test and open field test,and high-dose group was more efficient. As compared with the control group,the expression of 5-HT were significantly decreased in frontal cortex and hippocampus of the model group (P<0.05). As compared with the control group,the expressions of BDNF were significantly decreased in frontal cortex and hippocampus with the increasing concentration of MnCl2 which showed dose dependence(both P<0.05). The expressions of BDNFmRNA and TPH2mRNA in the treated group decreased significantly in frontal cortex and hippocampus in the treated group with the increasing concentration of manganese (both P<0.05)Conclusion:Chronic manganese poisoning could occur depression-like behavior in rats, and the depression might be associated with downregulating the expression of 5-HT and BDNF in the frontal cortex and hippocampus.