GAP‐43 mRNA in Rat Spinal Cord and Dorsal Root Ganglia Neurons: Developmental Changes and Re‐expression Following Peripheral Nerve Injury

Abstract

The expression of growth-associated protein GAP-43 mRNA in spinal cord and dorsal root ganglion (DRG) neurons has been studied using an enzyme linked in situ hybridization technique in neonatal and adult rats. High levels of GAP-43 mRNA are present at birth in the majority of spinal cord neurons and in all dorsal root ganglion cells. This persists until postnatal day 7 and then declines progressively to near adult levels (with low levels of mRNA in spinal cord motor neurons and 2000 - 3000 DRG cells expressing high levels) at postnatal day 21. A re-expression of GAP-43 mRNA in adult rats is apparent, both in sciatic motor neurons and the majority of L4 and L5 dorsal root ganglion cells, 1 day after sciatic nerve section. High levels of the GAP-43 mRNA in the axotomized spinal motor neurons persist for at least 2 weeks but decline 5 weeks after sciatic nerve section, with the mRNA virtually undetectable after 10 weeks. The initial changes after sciatic nerve crush are similar, but by 5 weeks GAP-43 mRNA in the sciatic motor neurons has declined to control levels. In DRG cells, after both sciatic nerve section or crush, GAP-43 mRNA re-expression persists much longer than in motor neurons. There was no re-expression of GAP-43 mRNA in the dorsal horn of the spinal cord after peripheral nerve lesions. Our study demonstrates a similar developmental regulation in spinal cord and DRG neurons of GAP-43 mRNA. We show moreover that failure of re-innervation does not result in a maintenance of GAP-43 mRNA in axotomized motor neurons.

Nerve growth factor‐mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor

“…While the expression of GAP-43 mRNA and protein is strongly upregulated in DRG neurons after peripheral nerve transection (Verge et al, 1990;Chong et al, 1992;Andersen and Schreyer, 1999), it has been shown that dorsal root injury does not induce GAP-43 expression in the affected DRG (Chong et al, 1994;Ramer et al, 2001;Schreyer and Skene, 1993). In this study, we report that uninjured cervical DRG from p75 ϩ/ϩ and p75 -/-adult mice display low levels of GAP-43 protein, reflecting the fact that GAP-43 expression in adult rat DRG is heterogeneous and reduced compared to neonatal levels (Chong et al, 1992;Verge et al, 1990). Twenty-eight days after rhizotomy, however, there was a clear increase in GAP-43 protein levels in both p75…”

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

“…GAP-43 is highly expressed in the embryonic and early postnatal spinal cord with almost undetectable levels by P29 [120]. Following peripheral conditioning lesions, lower motor neurons and dorsal root ganglia sensory neurons dramatically upregulate GAP-43 mRNA and levels remain elevated for 5 to 10 weeks [121]. This increase in GAP-43 expression does not occur following lesion of the central branch of dorsal root ganglia sensory neurons, suggesting a potential role for GAP-43 in the regenerative response, which occurs specifically following peripheral lesion [122].…”

Stimulating the Neurotrophic and Angiogenic Properties of Human Adipose-Derived Stem Cells Enhances Nerve Repair

“…We, therefore, examined the effect of stem cell transplantation on the expression of a number of genes known to be affected by peripheral nerve injury. Growth-associated protein GAP-43 is a molecule that is up-regulated in sciatic motor neurons and L4-L6 DRG neurons after sciatic nerve injury [55] and has been implicated as one of the several important mediators of peripheral nerve regeneration [6]. Typically, treatments such as electrical stimulation and growth factor administration, which stimulate regeneration, are associated with elevated levels of GAP-43 [56,57].…”