Schwartz M L, Shneidman P S, Bruce J, Schlaepfer W W
Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia 19104-6079.
J Neurosci Res. 1990 Oct;27(2):193-201. doi: 10.1002/jnr.490270209.
A coordinated up-regulation in the expression of all three neurofilament (NF) proteins occurs during postnatal development in the rat (Schlaepfer and Bruce, J Neurosci Res [in press], 1990a). In the present study, sciatic nerves were transected in neonatal rats in order to determine the effects of axotomy on the postnatal upregulation of NF expression in neurons of rat dorsal root ganglia (DRG). Left sciatic nerves were transected at postnatal day 3 (P3), 6 (P6), 8 (P8), or 10 (P10). mRNA and protein levels of the light (NF-L), mid-sized (NF-M), and heavy (NF-H) NF proteins were compared in L4 and L5 DRGs from the transected (left) vs. control (right) sides of the same animals at varying intervals after transection. When nerves were transected at P10, mRNA levels of all three NF proteins declined markedly in the parent DRG neurons, thereby completely interrupting the postnatal upregulation of NF expression. P10 transections also led to widespread chromatolytic changes in axotomized neurons, indistinguishable from those that occur in adult DRG following sciatic nerve transection (Goldstein et al., J Neurosci 7:1586-1594, 1987). Nerve transections at earlier (e.g., P3) neonatal timepoints also led to a decrease of NF expression, but to a lesser extent than that which resulted from a P10 transection. Also, P3 transections caused only minimal chromatolytic changes in the axotomized neurons. Thus, the postnatal upregulation of NF expression is dependent upon axonal continuity and the extent of axonal dependency increases during early postnatal development. These findings support the hypothesis that the postnatal upregulation of NF expression, the axotomy-induced downregulation of NF expression and the chromatolytic reaction to nerve transection are all dependent upon or responsive to axonal- or target cell-derived signals that are acquired during postnatal maturation.
大鼠出生后发育过程中，三种神经丝（NF）蛋白的表达会协同上调（施莱普费尔和布鲁斯，《神经科学研究》[即将发表]，1990年a）。在本研究中，为了确定轴突切断对新生大鼠背根神经节（DRG）神经元中NF表达的出生后上调的影响，对新生大鼠的坐骨神经进行了横断。在出生后第3天（P3）、6天（P6）、8天（P8）或10天（P10）切断左侧坐骨神经。在横断后的不同时间间隔，比较同一动物横断侧（左侧）与对照侧（右侧）L4和L5 DRG中轻链（NF-L）、中链（NF-M）和重链（NF-H）NF蛋白的mRNA和蛋白水平。当在P10切断神经时，所有三种NF蛋白的mRNA水平在亲代DRG神经元中显著下降，从而完全中断了NF表达的出生后上调。P10横断还导致轴突切断的神经元广泛出现染色质溶解变化，与成年DRG在坐骨神经横断后发生的变化无法区分（戈尔茨坦等人，《神经科学杂志》7:1586 - 1594，1987年）。在更早的新生时间点（如P3）切断神经也导致NF表达下降，但程度小于P10横断。此外，P3横断仅在轴突切断的神经元中引起最小程度的染色质溶解变化。因此，NF表达的出生后上调依赖于轴突连续性，并且在出生后早期发育过程中轴突依赖性的程度增加。这些发现支持了这样的假设，即NF表达的出生后上调、轴突切断诱导的NF表达下调以及对神经横断的染色质溶解反应都依赖于或响应出生后成熟过程中获得的轴突或靶细胞衍生信号。
