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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14572058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: NEMOTO Kiyomitsu University of Shizuoka, School of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (90189366)
• Project Period (FY): 2002 – 2004
• Keywords: Neurotrophin / Neurotrophin receptor / Cadmiun / Testis / Testicular damage / Gene expression

Research Abstract

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.