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The Journal of Neuroscience, September 1, 2002, 22(17):7493-7501
Dynamic Pattern of Reg-2 Expression in Rat Sensory Neurons after Peripheral Nerve Injury
Sharon Averill1, *, Danny R. Davis2, *, Peter J. Shortland1, John V. Priestley1, and Stephen P. Hunt2 1 Department of Neuroscience, Queen Mary University of London, London, E1 4NS, United Kingdom, and 2 Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom
The 16 kDa pancreatitis-associated protein Reg-2 has recently been shown to facilitate the regeneration of motor and sensory neurons after peripheral nerve injury in the adult rat. Reg-2 has also been shown to be a neurotrophic factor that is an essential intermediate in the pathways through which CNTF supports the survival of motor neurons during development. Here we report the dynamic expression of Reg-2 in rat sensory neurons after peripheral nerve injury. Reg-2 is normally not expressed by dorsal root ganglion (DRG) cells, but we show, using immunocytochemistry, that Reg-2 is rapidly upregulated in DRG cells after sciatic nerve transection and after 24 hr recovery is expressed almost exclusively in small-diameter neurons that bind the lectin Griffonia simplicifolia IB4 and express the purinoceptor P2X3. However, by 7 d after axotomy, Reg-2 is expressed in medium to large neurons and coexists partly with the neuropeptides galanin and neuropeptide Y, which are also upregulated after peripheral nerve transection. At this time point, Reg-2 is no longer expressed in small neurons, and there is no colocalization with IB4 binding neurons, demonstrating a shift in Reg-2 expression from one subset of DRG neurons to another. We also show by double labeling for activating transcription factor 3, a transcription factor that is upregulated after nerve injury, that Reg-2 expression occurs predominantly in axotomized DRG cells but that a small percentage of uninjured DRG cells also upregulate Reg-2. The selective expression within IB4/P2X3 cells, and the dynamic shift from small to large cells, is unique among DRG peptides and suggests that Reg-2 has a distinctive role in the injury response.
Key words: regeneration; axotomy; dorsal root ganglia; neuropeptide; peripheral nerve injury; Reg-2
* S.A. and D.R.D. contributed equally to this study.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177493-09$05.00/0
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