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GENE EXPRESSION AND REGULATION OF NEUROTROPHINS AND THEIR RECEPTORS IN PERIPHERAL NEUROPATHIES

周围神经病中神经营养因子及其受体的基因表达和调节

基本信息

批准号：
02807085
负责人：
SOBUE Gen
金额：
$ 1.15万
依托单位：
AICHI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02807085/
关键词：
Peripheral nerves neurotrophic factors NGF trk laminin sympathetic neuron sensory neuron 末梢神経障害神経成長因子 mRNA BDNF NTー3

项目摘要

Gene expression of the neurotrophic factors and their receptors and related molecules was analyzed in the human, rat and mouse peripheral nervous system, particularly in the process of the peripheral nerve degeneration and regeneration. The molecules analyzed in this study included NGF, BDNF, LNGFR, trk,trkB, laminin A, B_1, B_2 chains and collagen type I, III, IV. Expression levels of mRNA for these molecules in the tissues were determined by Northern blot analysis. The findings obtained are as follows :NGF, BDNF, LNGFR, laminin B_1, B_2, collagen type I, III, IV were synthesized in cultured Schwann cells inculture, and their mRNA levels were up- or down-regulated by exogenously administered cAMP analogues or by the contact with sensory neurons.Human DRG neurons and sympathetic neurons express LNGFR, trk, trkBmRNAs, and which were likely down-regulated in the cases with neuropathy particularly in axonal type.LNGFR were up- regulated and laminin B_1, B_2 were down-reglated in the axonal nerve lesions of humans as well as mouse and rats, but which were reversely reglated in associated with nerve regenerationNeurite arborization (sprouting) was significantly enhanced by NGF on the post-matured DRG neurons, and this ability was well retained in the aging process, which may have corresponded to the well preserved functional NGF receptor (trk) expression on the aged these neurous. Those finding confirmed that these neurotrophic molecules and their receptors are up-or down-regulated in association with peripheral nerve de-and regeneration suggesting their significant roles in the neuropathies. Further study on the signal mechanism for these gene expressions is now required.

分析了人、大鼠和小鼠周围神经系统，特别是周围神经变性和再生过程中神经营养因子及其受体及相关分子的基因表达。本研究分析的分子包括NGF、BDNF、lnfr、trk、trkB、层粘连蛋白A、B_1、B_2链和I型、III型、IV型胶原，通过Northern blot检测这些分子在组织中的mRNA表达水平。结果表明：在培养的雪旺细胞中可合成NGF、BDNF、lnfr、层粘连蛋白B_1、B_2、I型、III型、IV型胶原，外源性cAMP类似物或与感觉神经元接触可上调或下调其mRNA水平。人类DRG神经元和交感神经元表达lnfr、trk、trkbmrna，这些mrna在神经病变特别是轴突型患者中可能下调。NGF在人、小鼠和大鼠轴突神经损伤中表达lnfr上调，层粘连蛋白B_1、B_2下调，但与神经再生相关。NGF在成熟后DRG神经元上显著增强了神经突的生长（出芽）能力，且这种能力在衰老过程中保持良好，这可能与NGF受体（trk）在衰老后这些神经元上的功能表达保持良好有关。这些发现证实了这些神经营养分子及其受体的上调或下调与周围神经的去和再生有关，表明它们在神经病变中起着重要作用。这些基因表达的信号机制有待进一步研究。