Expression of the regeneration-associated protein SPRR1A in primary sensory neurons and spinal cord of the adult mouse following peripheral and central injury

Small proline-rich repeat protein 1A (SPRR1A) is expressed in dorsal root ganglion (DRG) neurons following peripheral nerve injury but it is not known whether SPRR1A is differentially expressed following injury to peripheral versus central DRG projections and a detailed characterisation of expression in sensory neuron sub-populations and spinal cord has not been performed. Here we use immunocytochemical techniques to characterise SPRR1A expression following sciatic nerve, dorsal root and dorsal column injury in adult mice. SPRR1A was not detected in naive spinal cord, DRG or peripheral nerves and there was minimal expression following injury to the centrally projecting branches of DRG neurons. However, following peripheral (sciatic) nerve injury, intense SPRR1A immunoreactivity was observed in the dorsal horn and motoneurons of the spinal cord, in L4/5 DRG neurons and in the injured nerve. A time-course study comparing expression following sciatic nerve crush and transection revealed maximum SPRR1A levels at day 7 in both models. However, while SPRR1A was down-regulated to baseline by 30 days post-lesion following crush injury, it remained elevated 30 days after transection. Cell-size and double-labelling studies revealed that SPRR1A was expressed by DRG cells of all sizes and co-localized with classical markers of DRG subpopulations and their primary afferent terminals. High co-expression of SPRR1A with activating transcription factor-3 and growth-associated protein-43 was observed, indicating that it is expressed by injured and regenerating neurons. This study supports the hypothesis that SPRR1A is a regeneration-associated gene and that SPRR1A provides a valuable marker to assess the regenerative potential of injured neurons.