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Development investigation for enhancement of regeneration and amelioration of function of the damaged peripheral nerves by medical regulation of neurotrophin synthesis.

通过神经营养蛋白合成的医学调节来增强受损周围神经的再生和改善功能的开发研究。

基本信息

批准号：
05557067
负责人：
FURUKAWA Shoei
金额：
$ 12.54万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

(1) EFFECTIVE IMPROVEMENT ON NEURONAL DYSFUNCTION BY ADMINISTRATION OF 4-METHYLCATECHOL (4-MC) IN DIABETIC OR ACRYLAMIDE-INDUCED PERIPHERAL NEUROPATHY.Streptozotocin (STZ) -induced diabetic rats showed a reduction in motor nerve conduction velocity (MNCV), myelinated axon diameter, and nerve growth factor (NGF) content in the sciatic nerve. 4-MC treatment started 4 weeks after the STZ injection resulted in improvements on all of these damages in diabetic rats. In acrylamide (ACR) -induced neuropathy, when ACR and 4-MC were coadministered intraperitoneallys, improved clinical signs, and more NGF content in the sciatic nerves, faster MNCV,and greater myelinated fiber density than in rats given ACR alone were found. These findings suggest that a decreased NGF level may be involved in the pathogenesis of diabetic and ACR-induced neuropathies and that 4-MC treatment could be a useful therapy.(2) PREPARATION OF ANTIBODIES SPECIFICALLY RECOGNIZE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NEUROTROPHIN-3 (NT-3).Quantitative methods to detect respective neurotrophins are necessary to evaluate theirroles in regeneration and functional repair of perigheral nerves. We succeeded to raise antibodies in chicken specifically recognize BDNF or NT-3. Two-site enzyme immunoassaies using these antibodies could detect BDNF and/or NT-3 as low as a concentration of a few pg/ml.(3) REGULATION OF BDNF EXPRESSION IN NEURONS CULTURED FROM CHICK DORSAL ROOT GANGLIA (DGR).Recent reports localize BDNF mRNA in the neurons cultured from chick embryo DRG,which are known responsive to BDNF.To estimate physiological roles of BDNF expression in the DRG neurons, we investigated changes of BDHF-like immunoreactivity during depolarization, and found that it caused a transient decrease in expression of BDNF protein. This suggests that stimuli-transmission followd by depolarization suppresses BDNF synthesis in DRG neurons during maturation of peripheral sensory system.

(1) 4-甲基儿茶酚（4-mc）可有效改善糖尿病或丙烯酰胺诱导的周围神经病变的神经元功能障碍。链脲佐菌素（STZ）诱导的糖尿病大鼠坐骨神经运动神经传导速度（MNCV）、髓鞘轴突直径和神经生长因子（NGF）含量降低。注射STZ后4周开始4- mc治疗，糖尿病大鼠的这些损伤均得到改善。在丙烯酰胺（ACR）诱导的神经病变中，与单独给予ACR的大鼠相比，当ACR和4-MC联合腹腔给药时，临床症状得到改善，坐骨神经中NGF含量增加，MNCV更快，有髓纤维密度更高。这些发现提示NGF水平的降低可能参与糖尿病和acr诱导的神经病变的发病机制，4-MC治疗可能是一种有用的治疗方法。(2)制备特异性识别脑源性神经营养因子（bdnf）和神经营养因子-3 （nt-3）的抗体。定量检测各神经营养因子在周围神经再生和功能修复中的作用是必要的。我们成功地在鸡体内培养了特异性识别BDNF或NT-3的抗体。使用这些抗体的两位点酶免疫测定可以检测低至几pg/ml的BDNF和/或NT-3。(3)鸡背根神经节（dgr）培养神经元中BDNF表达的调控。最近的报道将BDNF mRNA定位在鸡胚DRG培养的神经元中，这些神经元已知对BDNF有反应。为了估计BDNF表达在DRG神经元中的生理作用，我们研究了去极化过程中bdhf样免疫反应性的变化，发现它会导致BDNF蛋白表达的短暂下降。这表明刺激传递后去极化抑制了DRG神经元外周感觉系统成熟过程中BDNF的合成。