GAP-43 expression in primary sensory neurons following central axotomy

Abstract

Primary sensory neurons are capable of successful regenerative growth in response to peripheral nerve but not dorsal root injury. The present study is concerned with the differential expression of the mRNA for GAP-43, a growth-associated protein, in these sensory neurons, in response to injury of their central or peripheral axonal branches. Peripheral axotomy resulted in an elevation in message detectable within 24 hr, using Northern blot and in situ hybridization, which was maintained for 30 d, whereas dorsal root section produced no change except a transient and small increase if the axotomy was immediately adjacent to the dorsal root ganglia (DRG). Dorsal root section had no effect on GAP-43 mRNA levels in the dorsal horn or in neighboring intact DRG. It also failed to alter the laminar boundaries of the GAP-43 central terminal labeling produced by peripheral nerve section, even though vacant synaptic sites were produced in unstained laminae by this procedure. This indicates that the location of GAP-43 immunolabeling in the central terminals of primed sensory cells may not depend only on the location of vacant synaptic sites. We conclude that distinct control mechanisms regulate the response of DRG neurons to peripheral nerve and dorsal root injury, and these may be related both to the glial environment and the particular target influences exerted on the central and peripheral branches of the primary sensory neuron. Central denervation alone is insufficient to upregulate GAP-43 levels, and this may explain the relative absence of collateral sprouting after the production of central vacant synaptic sites. The failure of dorsal root section to increase GAP-43 expression may contribute to the poor regenerative response initiated by such lesions.

Early nerve regeneration after Achilles tendon rupture — a prerequisite for healing? A study in the rat

“…In fact, CGRP is known to have proinflammatory effects through vasodilation and promotion of protein extravazation [7,12]. In the proper tendinous tissue, GAP-immunoreactivity ernerged at week 1 post-rupture reflecting nerve ingrowth, which is consistent with reports on GAP protein levels in dorsal root ganglia after peripheral nerve injuries [5,9,36]. GAP may exert trophic actions by regulating growth cone motility and axon guidance signals [10,11].…”

Conditioning Injury-Induced Spinal Axon Regeneration Fails in Interleukin-6 Knock-Out Mice

“…GAP43 is widely expressed during axonal outgrowth in development but is significantly downregulated once pathfinding is complete (Dani et al, 1991;Reynolds et al, 1991). In the adult, GAP43 expression is significantly elevated in response to peripheral, but not central, axon lesions (Schreyer and Skene, 1991;Chong et al, 1994), and upregulated protein is transported along dorsal column axons (Schreyer and Skene, 1991). The differential response of GAP43 expression after injury has been associated with differential regenerative potential of PNS and CNS tissues.…”

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

“…Injured DRG neurons rapidly activate a transcriptional program of hundreds of genes as early as 1 day postinjury, and the majority of these exhibit sustained expression patterns by 2 weeks postinjury (141, 142) (140,141,(143)(144)(145)(146)(147)(148)(149). Because this gene expression program is not activated upon central axotomy, many groups have endeavored to promote CNS axon regeneration via the exogenous expression of regeneration associated genes or their upstream regulators (2,150).…”