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Stimulation of spinal cord regeneration by stimulator of NGF synthesis

NGF 合成刺激剂刺激脊髓再生

基本信息

批准号：
03454368
负责人：
FURUKAWA Yoshiko
金额：
$ 3.84万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454368/
关键词：
nerve growth factor NGF spinal cord degeneration of spinal cord regeneration of nerve NGF合成促進

项目摘要

Nerve growth factor (NGF) is a target derived trophic agent which promotes the survival and cellular metabolism of sympathetic neurons, neural crest-derived sensory neurons and basal forebrain cholinergic neurons. It is known that the proximal and/or distal stumps of severed nerve in the peripheral nervous system have an increase in NGF levels, and their responses as degeneration or neuronal cell death can be prevented with systemically administered exogenous NGF. The atrophy of cholinergic neurons in aged brain can be prevented with intraventricular administration of NGF. Although the spinal cord injury results the serious functional deficit, the specific function of NGF in the spinal cord is unknown.With the aim of gaining insight into the specific function of NGF in the spinal cord during degeneration/regeneration, we used the model of spinal cord transection, and determined temporal changes of NGF and NGFmRNA levels after the transection. As NGF displays a broad distribution in each segment (200 to 300 pg/g wet tissue) of spinal cord in young adult rat, we established the model of spinal cord transection (T-6) on 10-week-old Wistar rat. In the beginning at 2 days after transection (2d), NGF displays a significant increase at the rostral stump of transection site (p<0.01). Then, at both (rostral and caudal) stumps, the level of NGF significantly increase 2 to 3-folds at 4d, 2 to 4-folds at 6d. The significant increases of NGF at both stumps are detected from 4d through 8d, and those at the rostral stump are detected from 2d through 21d. At the both stumps, the expression of NGF mRNA increase at 1d,then gradually decrease from 2d though 8d. The increase of NGF and NGFmRNA levels in the both stumps are stimulated by the administration of catechol compound, which is known to be a stimulator of NGF synthesis in cell culture or peripheral nervous system. These results suggest that NGF may play an important role in the regeneration of spinal cord.

神经生长因子（nerve growth factor，NGF）是一种靶向营养因子，能促进交感神经元、脊神经源性感觉神经元和基底前脑胆碱能神经元的存活和细胞代谢。已知周围神经系统中切断神经的近端和/或远端残端具有NGF水平的增加，并且它们作为变性或神经元细胞死亡的反应可以用全身施用的外源性NGF来预防。脑室内注射神经生长因子可防止老年脑胆碱能神经元的萎缩。虽然脊髓损伤会导致严重的功能障碍，但NGF在脊髓中的具体功能尚不清楚，为了深入了解NGF在脊髓变性/再生过程中的具体功能，我们采用脊髓横断模型，测定了脊髓横断后NGF及其mRNA水平的时间变化。由于NGF在幼年大鼠脊髓各节段中分布广泛（200 ~ 300 pg/g湿组织），我们在10周龄Wistar大鼠上建立了脊髓横断（T-6）模型。在切断后第2天（2d）开始，切断部位的嘴侧残端的NGF显示出显著的增加（p<0.01）。随后，在头端和尾端，NGF水平在4d时显著增加2 - 3倍，在6d时增加2 - 4倍。两个断端的NGF在4 ~ 8d显著增加，而吻端的NGF在2 ~ 21 d显著增加。在断肢两侧，NGF mRNA表达在第1天开始增加，第2 ~ 8天逐渐下降。通过给予儿茶酚化合物刺激两个残肢中NGF和NGFmRNA水平的增加，已知儿茶酚化合物是细胞培养物或外周神经系统中NGF合成的刺激剂。提示NGF在脊髓再生中可能起重要作用。