Shi Tie-Jun Sten, Huang Ping, Mulder Jan, Ceccatelli Sandra, Hokfelt Tomas
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Neurosignals. 2009;17(3):203-12. doi: 10.1159/000210400. Epub 2009 Apr 4.
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 immunohistochemical study we have monitored phosphorylated Akt (p-Akt) levels in adult mouse DRGs and spinal cord following unilateral peripheral sciatic nerve transection (axotomy) or carrageenan-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 increased in intensity in the ipsilateral spinal dorsal horn after axotomy and expanded into deeper layers. Carrageenan-induced 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.
Akt已被证实在包括背根神经节(DRG)和脊髓运动神经元在内的多种细胞类型中具有促生存和抗凋亡活性。在这项免疫组织化学研究中,我们监测了成年小鼠DRG和脊髓在单侧坐骨神经切断术(轴突切断术)或角叉菜胶诱导的炎症后磷酸化Akt(p-Akt)的水平。在对照动物中,大约一半的腰段DRG神经元轮廓(NP),主要是中小型神经元,呈p-Akt免疫反应性(IR),其中约50%表达降钙素基因相关肽和/或异凝集素IB4。轴突切断术后两周,p-Akt阳性NP的数量仅略有减少,但p-Akt免疫荧光强度显著增加。同侧p-Akt-IR NP中有三分之一为甘丙肽阳性,但几乎不与神经肽Y共定位。此外,轴突切断术后同侧脊髓背角p-Akt样免疫反应性强度显著增加,并扩展到更深层。角叉菜胶诱导的外周炎症在1小时后增加了p-Akt-IR NP的数量。轴突切断术和炎症均导致DRG神经元核p-Akt样免疫反应性明显增加。我们的研究结果支持Akt作为外周损伤后感觉神经元和脊髓中的关键信号分子发挥作用。