Axonal dependency of the postnatal upregulation in neurofilament expression.

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.