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

本研究分析了神经营养因子及其受体和相关分子在人、大鼠和小鼠周围神经系统中的基因表达，特别是在周围神经退行性变和再生过程中的表达。本研究分析的分子包括NGF、BDNF、LNGFR、Trk、TrkB、层粘连蛋白A、B_1、B_2链和I、III、IV型胶原。结果表明：培养的雪旺细胞可合成NGF、BDNF、LNGFR、层粘连蛋白B_1、B_2、I、III、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。人背根神经节神经元和交感神经元表达LNGFR、trk、trkBmRNAs，在神经病患者中表达下调，尤其是轴索型。在人、小鼠和大鼠的轴索神经损伤中，LNGFR表达上调，B_1、B_2表达下调NGF能显著促进成熟后DRG神经元的树枝(出芽)，这种能力在衰老过程中被很好地保留下来，这可能与NGF受体(Trk)在这些神经元上的表达完好有关。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破坏和再生有关，这表明它们在神经疾病中发挥着重要作用。现在需要进一步研究这些基因表达的信号机制。

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.