Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neurosignals 2009;17:203–212 DOI: 10.1159/000210400 Expression of p-Akt in Sensory Neurons and Spinal Cord after Peripheral Nerve Injury Tie-Jun Sten Shi a, b Ping Huang a Jan Mulder a Sandra Ceccatelli a Tomas Hökfelt a a Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; b Department of Life Sciences and Engineering, Bio-X Center, Harbin Institute of Technology, Harbin, China axotomy and expanded into deeper layers. Carrageenan-in- duced peripheral inflammation increased the number of p- Akt-IR NPs after 1 h. Both axotomy and inflammation caused a clear increase in nuclear p-Akt-like immunoreactivity in DRG neurons. Our findings support a role for Akt as a key signaling molecule in sensory neurons and spinal cord after peripheral injury. Copyright © 2009 S. Karger AG, Basel Introduction Primary sensory neurons synthesize a large number of signaling molecules involved in the transmission and modulation of nociceptive information from the periph- eral to the central nervous system [1]. A well-known as- pect of sensory neurons is the remarkable chemical plas- ticity following peripheral nerve injury [1–6], as also shown in more recent array studies [7–9]. Thus, after nerve injury the phenotype of sensory neurons is markedly changed, which may be important for regeneration/sur- vival and development of neuropathic pain for example. Akt, also known as protein kinase B, is a serine/threo- nine kinase with sequence homology to protein kinases A and C [10, 11] . As a key downstream substrate in the phosphatidyl-inositol 3-kinase (PI3-K) pathway, Akt plays important roles in various biological processes, in- Key Words Dorsal root ganglion  Inflammation  Neuropeptide  Nuclear translocation  Pain  Spinal cord Abstract Akt has been implicated in pro-survival and anti-apoptotic activities in many cell types, including dorsal root ganglion (DRG) and spinal motor neurons. In this immunohistochem- ical study we have monitored phosphorylated Akt (p-Akt) levels in adult mouse DRGs and spinal cord following unilat- eral peripheral sciatic nerve transection (axotomy) or carra- geenan-induced inflammation. In control animals around half of the lumbar DRG neuron profiles (NPs), mainly small and medium-sized ones, were p-Akt immunoreactive (IR), and of these around 50% expressed calcitonin gene-related peptide and/or isolectin IB4. Two weeks after axotomy, the number of p-Akt-positive NPs was only slightly reduced, but p-Akt immunofluorescence intensity was strongly increased. One third of the ipsilateral p-Akt-IR NPs was galanin positive, but virtually without colocalization with neuropeptide Y. Furthermore, p-Akt-like immunoreactivity significantly in- creased in intensity in the ipsilateral spinal dorsal horn after Received: December 12, 2008 Accepted after revision: January 19, 2009 Published online: April 4, 2009 Dr. Tie-Jun Shi Department of Neuroscience, Karolinska Institutet SE–171 77 Stockholm (Sweden) Tel. +46 8 5248 7067, Fax +46 8 331 692 E-Mail tiejun.shi@ki.se or tiejun_shi@hit.edu.cn © 2009 S. Karger AG, Basel 1424–862X/09/0173–0203$26.00/0 Accessible online at: www.karger.com/nsg This study is dedicated to Prof. Ji-Sheng Han on the occasion of his 80th birthday.