Heumann R, Lindholm D, Bandtlow C, Meyer M, Radeke M J, Misko T P, Shooter E, Thoenen H
Department of Neurochemistry, Max Planck Institute for Psychiatry, Martinsried, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8735-9. doi: 10.1073/pnas.84.23.8735.
In newborn rats the levels of nerve growth factor (NGF) mRNA (mRNANGF) and NGF receptor mRNA (mRNA(rec)) in the sciatic nerve were 10 and 120 times higher, respectively, than in adult animals. mRNA(rec) 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 nerve 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. mRNA(rec) levels were also markedly elevated distal to the transection site, in agreement with previous results obtained by immunological methods [Taniuchi, M., Clark, H. B. & Johnson, E. M., Jr. (1986) Proc. Natl. Acad. Sci. USA 83, 4094-4098]. Following a crush lesion (allowing regeneration), the mRNA(rec) 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 mRNA(rec) over the time period studied. Changes in mRNANGF and mRNA(rec) occurring in vivo after transection were compared with those observed in pieces of sciatic nerve kept in culture. No difference was found for mRNA(rec). 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 mRNA(rec) synthesis is determined by axonal contact.
在新生大鼠中，坐骨神经中神经生长因子（NGF）mRNA（mRNANGF）和NGF受体mRNA（mRNA(rec)）的水平分别比成年动物高10倍和120倍。mRNA(rec)水平从出生后开始稳步下降，在出生后第三周接近成年水平，而mRNANGF水平仅在出生后第一周后下降，尽管在第三周时也达到成年水平。成年坐骨神经横断后，mRNANGF随时间呈明显的双相增加。在切口近端，这种增加局限于紧邻切口的区域；在周围，所有节段均出现类似的双相增加。mRNA(rec)水平在横断部位远端也明显升高，这与先前通过免疫学方法获得的结果一致[Taniuchi, M., Clark, H. B. & Johnson, E. M., Jr. (1986) Proc. Natl. Acad. Sci. USA 83, 4094 - 4098]。在挤压损伤（允许再生）后，随着再生神经纤维穿过远端节段，mRNA(rec)水平迅速下调。mRNANGF在再生过程中也发生下调，但在所研究的时间段内，其下调速度较慢且程度不如mRNA(rec)。将横断后体内发生的mRNANGF和mRNA(rec)变化与培养的坐骨神经片段中观察到的变化进行比较。对于mRNA(rec)未发现差异。在培养中仅出现mRNANGF最初的快速增加，但通过添加活化巨噬细胞可模拟体内情况。这反映了体内神经损伤后巨噬细胞浸润华勒氏变性区域的情况。这些结果表明，坐骨非神经元细胞中mRNANGF的合成受巨噬细胞调节，而mRNA(rec)的合成由轴突接触决定。
