Induction of nerve growth factor receptor in Schwann cells after axotomy.

Abstract

We have discovered that axotomy of sciatic nerve induces Schwann cells distal to the lesion to express de novo, or at greatly increased levels, receptors for nerve growth factor (NGF). Surgical transection of sciatic nerve was performed on adult Sprague-Dawley rats, and, at various times after the operation, the following tissues were dissected for quantitation of NGF receptor: L4 and L5 dorsal root ganglia, sciatic nerve proximal to the transection, sciatic nerve distal to the transection, tibialis anterior muscle, and skin of the dorsum of the foot. The NGF receptor content of these samples was determined by labeling receptor molecules with radioiodinated NGF (1251-NGF) and then specifically immunoprecipitating the 125I-NGF-receptor complexes with 192-IgG, a monoclonal antibody directed against the rat NGF receptor. We observed a time-dependent increase in the amount of radioligand-labeled NGF receptor proteins found in the distal segment of transected sciatic nerve; by 7 days the density of receptor (crosslinked '251-NGF molecules per mg of homogenate protein) had increased at least 50-fold. The number of receptor molecules in tibialis anterior muscle and dorsal foot skin, two structures denervated by the transection, also increased, with time courses parallel to that of distal sciatic nerve. There was little increase in the density of NGF receptors in the sciatic nerve proximal to the lesion and in the dorsal root ganglia. Immunohistochemical examination of the distal portion of transected sciatic nerve and of the muscle, with 192-IgG as the primary ligand, revealed prominent and exclusive staining of apparently all Schwann cells of the endoneurium, indicating that these peripheral neuroglial cells were expressing NGF receptors. These results show that axonal damage can induce the expression of NGF receptors in the population of sheath cells thought to promote neuronal regeneration. This dramatic increase in NGF receptors may be a mechanism to facilitate the regeneration of NGF-responsive neurons.Nerve growth factor (NGF) is a polypeptide neurotrophic agent that promotes the survival and function of sympathetic neurons and neural crest-derived sensory neurons (1). NGF also exerts chemotactic, or tropic, activity on sensory neurons (2, 3). These biological actions of NGF are initiated by the specific binding of the protein to cell-surface receptor molecules (4). In addition to sympathetic and sensory neurons, the NGF receptor has been found on several nonneuronal cells, including the clonal rat pheochromocytoma PC12 cells (5) and the A875 clonal line of human melanoma (6). Schwann cells, the peripheral neuroglial cells that ensheath nerve axons, also express NGF receptors when placed into tissue culture during a restricted period of embryogenesis (7-11); a subpopulation of Schwann cells from cultured embryonic chicken dorsal root ganglia (DRG) displays specific binding of NGF during embryonic days 6-12 (8). NGF receptors have not been detected on Schwann cells in vivo, and the function of the recept...

Guidance of regenerating motor axons in larval and juvenile bullfrogs

“…It has recently been reported that the levels of NGF and its mRNA increase in the distal stump of rat peripheral nerve within a few days of nerve transection (Korsching et al, 1986), and that all Schwann cells in the stump markedly increase their expression of low-affinity NGF receptors during this period (Taniuchi et al, 1986). Taniuchi et al (1986) propose that NGF binds to cell-surface receptors of denervated Schwann cells and is subsequently transferred to the NGF receptors of regenerating axons.…”

“…Taniuchi et al (1986) propose that NGF binds to cell-surface receptors of denervated Schwann cells and is subsequently transferred to the NGF receptors of regenerating axons. By this means, Schwann cells could provide both trophic support and tropic guidance to regenerating axons of NGFsensitive neurons, and, by expression of as-yet-unidentified agents, to axons of other neurons as well.…”

Activation of Rac GTPase by p75 Is Necessary for c-junN-Terminal Kinase-Mediated Apoptosis

“…4). It is well documented in the literature that p75 is robustly induced in neurons, Schwann cells, and oligodendrocytes after injuries (Taniuchi et al, 1986;Koliatsos et al, 1991;Hayes et al, 1992;Roux et al, 1999). For instance, p75 has been reported to be induced in dying neurons after a seizure (Roux et al, 1999) and ischemia (Park et al, 2000) and in cortical neurons after experimental allergic encephalomyelitis (Calza et al, 1997;Nataf et al, 1998).…”

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

“…Functionally, macrophage activation within the DRG and peripheral nerve following peripheral nerve injury is known to help remove degenerating neuronal debris and myelin as well as contribute to subsequent regeneration (Lu and Richardson 1993, Perry and Brown 1992, Hu and McLachlan 2002. Recently, it has been recognized that inflammatory responses in the DRG may also contribute to the development pathological pain states (Cui et al, 2000;Xie et al, 2006) through the release of a variety of proinflammatory factors which are capable of sensitizing primary afferent neurons whose cell bodies are housed in the DRG (Taniuchi et al, 1986;Lindholm et al, 1987;Meyer et al, 1992;Hammarberg et al, 1996;Ma & Eisenach, 2002.…”