Wong Liang-Fong, Yip Ping K, Battaglia Anna, Grist John, Corcoran Jonathan, Maden Malcolm, Azzouz Mimoun, Kingsman Susan M, Kingsman Alan J, Mazarakis Nicholas D, McMahon Stephen B
Oxford BioMedica (UK) Ltd., Medawar Centre, Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
Nat Neurosci. 2006 Feb;9(2):243-50. doi: 10.1038/nn1622. Epub 2005 Dec 25.
The embryonic CNS readily undergoes regeneration, unlike the adult CNS, which has limited axonal repair after injury. Here we tested the hypothesis that retinoic acid receptor beta2 (RARbeta2), critical in development for neuronal growth, may enable adult neurons to grow in an inhibitory environment. Overexpression of RARbeta2 in adult rat dorsal root ganglion cultures increased intracellular levels of cyclic AMP and stimulated neurite outgrowth. Stable RARbeta2 expression in DRG neurons in vitro and in vivo enabled their axons to regenerate across the inhibitory dorsal root entry zone and project into the gray matter of the spinal cord. The regenerated neurons enhanced second-order neuronal activity in the spinal cord, and RARbeta2-treated rats showed highly significant improvement in sensorimotor tasks. These findings show that RARbeta2 induces axonal regeneration programs within injured neurons and may thus offer new therapeutic opportunities for CNS regeneration.
与成体中枢神经系统不同，胚胎中枢神经系统很容易发生再生，而成体中枢神经系统在损伤后轴突修复能力有限。在此，我们检验了以下假说：视黄酸受体β2（RARβ2）在神经元生长发育过程中起关键作用，它可能使成体神经元在抑制性环境中生长。在成年大鼠背根神经节培养物中过表达RARβ2可提高细胞内环磷酸腺苷水平并刺激神经突生长。在体外和体内，背根神经节神经元中稳定表达RARβ2能使其轴突跨越抑制性的背根进入区再生，并投射到脊髓灰质中。再生的神经元增强了脊髓中二级神经元的活性，经RARβ2处理的大鼠在感觉运动任务中表现出显著改善。这些发现表明，RARβ2可诱导受损神经元内的轴突再生程序，因此可能为中枢神经系统再生提供新的治疗机会。
