The axotomy response
Peripheral nerve injury results in profound alterations of neuronal metabolism, survival, transmitter phenotype and regenerative capacity (Klimaschewski et al., 1996b; Fu and Gordon, 1997). This ‘axotomy-response’ is contributed by transcriptional changes triggered by the loss of trophic support from target organs and by signals generated at the injury site. Primary neurons derived from peripheral ganglia are particularly suitable to study regeneration-associated gene expression in response to either denervation from peripheral targets or from the central nervous system where the preganglionic neurons are located and the sensory afferents terminate, respectively (Klimaschewski et al., 1996a).
The switch from normal ‘transmission mode’ to ‘regenerating growth mode’ in response to peripheral nerve lesion is possibly triggered by interruption of retrogradely transported signals, since blockade of axonal transport in vivo is sufficient to induce elongating axon growth in adult sensory neurons which is typically observed after peripheral (sciatic or spinal nerve) but not after central (nerve root) lesion (Smith and Skene, 1997). To identify genes involved in this differential growth response by adult sensory neurons after injury we have analyzed the gene expression profiles of rat dorsal root ganglia three days after either dorsal root or spinal nerve compression at the level of lumbar L5 applying 230A Affymetrix microarray chips. They currently provide the most rapid and comprehensive screen for differential gene expression.
Extensive data analysis revealed a limited number of genes up- or down-regulated more than twofold in response to nerve root and spinal nerve lesion, respectively. Quantitative RT-PCR confirmed the regulation of genes associated with neuronal survival, axon regeneration and local inflammation. The present data reveal a complex response of dorsal root ganglia to nearby axonal crush lesions which is partially identical to the gene expression profile obtained after peripheral nerve transection (Costigan et al., 2002). However, significant differences, particularly after nerve root lesion, were observed which may explain the reduced growth rate of root axons when compared to the rapid regeneration of lesioned spinal nerve axons.
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