Study on Expression and Function of Neurotrophins and their Receptors in Non-Neuronal Tissues

本研究旨在阐明神经营养因子（NGF、BDNF、NT-3和NT-4）在非神经元组织中的作用。因此，在镉给药诱导的睾丸损伤过程中，评估了神经营养因子及其受体的基因表达，镉对睾丸具有潜在的毒性作用，如下所示。(1)在7周龄SD大鼠和ddy小鼠睾丸中检测神经营养因子及其受体基因表达的时间变化，注射20 μmol/kg CdCl_2。结果表明，注射后48-96小时，大多数基因的表达随睾丸细胞损伤的出现而变化。(2)用CdCl_2单次（s.c.）注射0、5、10、15和20 μmol/kg CdCl_2。当剂量超过15 μmol/kg时，可引起睾丸细胞基因表达的改变和睾丸细胞的损伤。(3)在不同年龄（3、7和12周龄）的SD大鼠中，在给予单次（s.c.）注射0、5、10、15和20 μmol/kg CdCl_2。在3和7周龄大鼠中观察到超过15 μmol/kg剂量的基因表达变化，而在12周龄大鼠中观察到超过10 μmol/kg剂量的基因表达变化。睾丸细胞的损伤也呈现出类似的趋势，总之，神经营养因子及其受体的基因表达随着时间、剂量和年龄的变化而变化，与镉诱导的睾丸细胞损伤的出现相一致。这些结果提出了神经营养因子参与其毒性机制的可能性。深入研究神经促甲状腺激素在镉毒性中的作用，对于了解其在睾丸中的功能具有重要意义。

The present study aimed to clarify the roles of neurotrophins (NGF, BDNF, NT-3 and NT-4) in non-neuronal tissues. Therefore, the gene expression of neurotrophins and their receptors was assessed during the process of testicular injury induced by administration of cadmium, which has potent toxic effects on the testis, as below.(1) Temporal changes in the gene expression of neurotrophins and their receptors were examined in the testes of 7 week-old SD rats and ddy mice given a single (s.c.) injection of 20 μmol/kg CdCl_2. The results indicated that the expression of the most genes changed in accordance with the appearance of the testicular cell damage, 48-96 hr after the injection.(2) A dose effect of CdCl_2 on their testicular gene expression was examined in the 7 week-old SD rats and ddy mice 96 hr after given a single (s.c.) injection of 0, 5, 10, 15 and 20 μmol/kg CdCl_2. The administration of more than 15 μmol/kg induced the expressional changes in their genes and testicular cell damage.(3) Expression of their testicular gene expression was evaluated in the SD rats of different ages (3, 7 and 12 week-old) 96 hr after given a single (s.c.) injection of 0, 5,10,15 and 20 μmol/kg CdCl_2. The changes in the gene expression were observed in 3 and 7 week-old rats administered more than 15 μmol/kg, whereas they were observed in 12 week-old rats administered more than 10 μmol/kg. The testicular cell damage indicated the similar tendency.In summary, the gene expression of neurotrophins and their receptors changed with time-, dose-, and age-dependencies in accordance with the appearance of cadmium-induced testicular cell damage. These results raise the possibility that neurotrophins are involved in its toxicity mechanism. To further study on the role of neurotrphins in the toxicity of cadmium would be of importance in understanding their functions in the testis.