| Objectives: Lead acetate is a kind of toxic metal and contributes to the damages of functions of many systems especially nervous system. Nerve grows factor (NGF) and brain-derived neurotropic factor (BDNF), as one of the important active molecules, belong to neurotrophic family, which can affect the development of neuron and prevent neuron from damage. The expression of NGF and BDNF can be regulated by many factors, such as the nervous system diseases, the injury of brain, etc. NGF and BDNF play various roles through the combination with their relative receptors. As NGF and BDNF low affinity receptor, P75 plays different physiological or/and pathological roles by combining with different ligands. Many studies showed lead acetate affected the function of endocrine system. Thyroid hormones (TH) can affect the functions of many other systems, especially nerve system. TH has physiological and pathological effects on the developing and developed brain through regulating its response genes expression. TH can regulate the expression of NGF and BDNF as its response genes. The present study explores the effects of lead on the expression of NGF and BDNF as well as their receptor (P75) and the regulation of TH. This paper will reveal the neurotoxic mechanism of lead from a new point of view ----neuroendocrine.Methods1 Lead acetate was given to SD rats intraperitoneal injection (ip) for 5 days at the dosage of 25,50 and 100mg/kg body weight, respectively. The contents of lead in serum, cerebral cortex and hippocampus were measured by atomic absorption spectrophotometer. Triiodothyronine (T3), thyroxin (T4), TSH in serum and T3, T4 in cerebral cortex and hippocampus were determined by radio immunoassys (RIAs). This part is to study the effects of lead acetate on the levels of thyroid hormones in serum and brain of rat.2 The levels of NGF mRNA and BDNF mRNA expression in cerebral cortex and hippocampus were observed by RT-PCR. The expression of NGF and BDNF protein in cerebral cortex and hippocampus were determined by immunohistochemistry. This part is to study the effects of lead acetate on the expression of NGF and BDNF in rat cerebral cortex and hippocampus.3 The expression of P75 protein in cerebral cortex and hippocampus was determined by immunohistochemistry. This part is to study the effects of lead acetate on the expression of neurotrophic factors receptor (P75NGFR) in rat cerebral cortex and hippocampus. 4 6-n-propyl-2-thiouracil (PTU) was used to make a hypothyroid model and then lead acetate was given at the dosage of 50mg/kg body weight through ip. for 5 days, the expression of NGF and BDNF protein in the cerebral cortex and hippocampus were determined by immunohistochemistry. This part is to observe the effects of lead on NGF and BDNF protein expression in hypothyroid rat brain and explore the regulation of thyroid hormone to the effects of lead on NGF and BDNF protein expression in rat brain.Results 1 Compared with the control group, the contents of lead were significantly increased in serum, cerebral cortex and hippocampus in the treatment groups, respectively (P<0.01, P<0.05, P<0.01), and there was a good dose-response relationship. The levels of T3,T4 in the serum were significantly decreased while TSH increased in every treatment group compared with the control (P<0.01, P<0.01, P<0.05) and there was a good dose-response relationship. The levels of T3,T4 in cerebral cortex were significantly decreased in every treatment group compared with the control(P<0.05, P<0.01), while the level of T4 had a decreased tendency(P>.05) and the level of T3 had no significant difference in hippocampus (P>0.05). Correlation analysis demonstrated that the contents of lead in cerebral cortex and hippocampus were positively correlated with that in serum and negatively correlated with the levels of T3, T4 in cerebral cortex and hippocampus, respectively. 2 The results of RT-PCR showed that the expression of NGF mRNA and BDNF mRNA were significantly increased in cerebral cortex and hippocampus...
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