DIFFERENTIAL REGULATION OF MESSENGER-RNA ENCODING NERVE GROWTH-FACTOR AND ITS RECEPTOR IN RAT SCIATIC-NERVE DURING DEVELOPMENT, DEGENERATION, AND REGENERATION - ROLE OF MACROPHAGES
DIFFERENTIAL REGULATION OF MESSENGER-RNA ENCODING NERVE GROWTH-FACTOR AND ITS RECEPTOR IN RAT SCIATIC-NERVE DURING DEVELOPMENT, DEGENERATION, AND REGENERATION - ROLE OF MACROPHAGES
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DOI：
10.1073/pnas.84.23.8735
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发表时间：
1987-12-01
影响因子：
11.1
通讯作者：
THOENEN, H
中科院分区：
文献类型：
--
作者：
HEUMANN, R;LINDHOLM, D;THOENEN, H
新生大鼠坐骨神经中神经生长因子（NGF） mRNA （mRNANGF）和NGF受体mRNA （mRNArec）水平分别比成年大鼠高10倍和120倍。mRNArec水平从出生开始稳步下降，在出生后第三周接近成人水平，而mRNANGF水平仅在出生后第一周后下降，尽管也在第三周达到成人水平。横断成人坐骨神经导致mRNANGF随时间明显双相增加。在切口的近端，这种增加仅限于紧挨着切口的区域；在周围，所有节段均出现类似的双相增加。在横切部位的远端，mRNArec水平也显著升高，这与之前通过免疫学方法获得的结果一致[Taniuchi， M., Clark， H.B.和Johnson， e.m., Jr. (1986) Proc. Natl.]。学会科学。[j]。在挤压损伤后（允许再生），当再生的神经纤维穿过远端节段时，mRNArec水平迅速下调。mRNANGF的下调也发生在再生过程中，但在研究的时间段内，mRNANGF的下调速度较慢，也没有mRNArec的下调那么广泛。将横断后体内mRNANGF和mRNArec的变化与培养坐骨神经片的变化进行比较。mRNArec没有发现差异。mRNANGF仅在培养中出现最初的快速增加，但体内情况可以通过添加活化的巨噬细胞来模拟。这反映了在体内，神经病变后，巨噬细胞浸润到沃勒氏变性区。这些结果表明，坐骨非神经元细胞中mRNANGF的合成受巨噬细胞的调节，而mRNArec的合成受轴突接触的影响。
In newborn rats the levels of nerve growth factor (NGF) mRNA (mRNANGF) and NGF receptor mRNA (mRNArec) in the sciatic nerve were 10 and 120 times higher, respectively, than in adult animals. mRNArec levels decreased steadily from birth, approaching adult levels by the third postnatal week, whereas mRNANGF levels decreased only after the first postnatal week, although also reaching adult levels by the third week. Transection of the adult sciatic nerves resulted in a marked biphasic increase in mRNANGF with time. On the proximal side of the cut, this increase was confined to the area immediately adjacent to the cut; peripherally, a similar biphasic increase was present in all segments. mRNArec levels were also markedly elevated distal to the transection site, in agreement with previous results obtained by immunological methods [Taniuchi, M., Clark, H.B. and Johnson, E. M., Jr. (1986) Proc. Natl. Acad. Sci. USA 83, 4094-4098]. Following a crush lesion (allowing regeneration), the mRNArec levels were rapidly down-regulated as the regenerating nerve fibers passed through the distal segments. Down-regulation of mRNANGF also occurred during regeneration but was slower and not as extensive as that of mRNArec over the time period studied. Changes in mRNANGF and mRNArec occurring in vivo after transection were compared with those observed in pieces of sciatic nerve kept in culture. No difference was found for mRNArec. Only the initial rapid increase in mRNANGF occurred in culture, but the in vivo situation could be mimicked by the addition of activated macrophages. This reflects the situation in vivo where, after nerve lesion, macrophages infiltrate the area of the Wallerian degeneration. These results suggest that mRNANGF synthesis in sciatic non-neuronal cells is regulated by macrophages, whereas mRNArec synthesis is determined by axonal contact.