Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Neurosci Lett. 2011 Feb 18;490(1):41-5. doi: 10.1016/j.neulet.2010.12.022. Epub 2010 Dec 16.
Previous studies demonstrated that nuclear factor κB (NF-κB) activation is decreased in dorsal root ganglia (DRG) of rats having streptozotocin (STZ)-induced diabetes. DRG contain cell bodies of neurons that convey sensory signals from the periphery. To determine the relationship between diabetes-induced neuropathy and NF-κB expression in DRG, behavioral, immunohistochemical, and biochemical studies were performed on naïve and 3-month diabetic rats. Behavioral studies confirmed that many diabetic rats develop tactile allodynia, or increased sensitivity to light touch, in the hind paws. Immunohistochemical studies on lumbar DRG that receive input from the affected regions revealed that p50 and p65, frequent NF-κB subunit partners, are differentially localized. Intense p65 immunostaining was detected in the cytoplasm of small- and medium-sized neurons as well as in satellite cells. In contrast, p50 was localized in the cytoplasm of virtually all neurons. In many cases, prominent staining was also present in nuclei, a location consistent with transcription factor activation. Immunohistochemical and biochemical studies found that the nuclear to cytoplasmic ratio of p50 expression was significantly reduced in diabetic rats compared to that in naïve animals. Our findings raise the possibility that changes in NF-κB activation in a subset of DRG neurons participates in mediating diabetes-induced sensory neuropathy.
先前的研究表明,链脲佐菌素(STZ)诱导的糖尿病大鼠背根神经节(DRG)中核因子 κB(NF-κB)的激活减少。DRG 包含神经元的细胞体,这些神经元将来自外周的感觉信号传递到中枢神经系统。为了确定糖尿病诱导的周围神经病变与 DRG 中 NF-κB 表达之间的关系,对未处理的和 3 个月的糖尿病大鼠进行了行为学、免疫组织化学和生化研究。行为学研究证实,许多糖尿病大鼠在后爪中出现触觉过敏,即对轻触的敏感性增加。对接收受影响区域传入信号的腰椎 DRG 的免疫组织化学研究表明,p50 和 p65(NF-κB 常见的亚基伙伴)的定位不同。在小和中型神经元以及卫星细胞的细胞质中检测到强烈的 p65 免疫染色。相比之下,p50 定位于几乎所有神经元的细胞质中。在许多情况下,核内也存在明显的染色,这与转录因子的激活一致。免疫组织化学和生化研究发现,与未处理的动物相比,糖尿病大鼠 DRG 神经元中 p50 表达的核质比显著降低。我们的研究结果提出了一种可能性,即 DRG 神经元中 NF-κB 激活的变化可能参与介导糖尿病诱导的感觉性周围神经病。