Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury
Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury
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DOI：
10.1523/jneurosci.23-10-04117.2003
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发表时间：
2003-05-15
影响因子：
5.3
通讯作者：
Noguchi, K
中科院分区：
文献类型：
--
作者：
Obata, K;Yamanaka, H;Noguchi, K
为探讨初级传入神经元中脑源性神经营养因子（BDNF）基因表达的细胞内信号转导途径，我们检测了外周炎症和坐骨神经切断后背根神经节（DRG）神经元中细胞外信号调节蛋白激酶（ERK）的激活。外周炎症诱导ERK磷酸化的增加，主要是在酪氨酸激酶A含有小到中等直径的DRG神经元。丝裂原活化蛋白激酶（MAPK）激酶1/2抑制剂U 0126的治疗逆转了完全弗氏佐剂诱导的痛敏性和DRG神经元中磷酸化ERK（p-ERK）和BDNF的增加。另一方面，轴突切断诱导ERK的激活主要在中型和大型DRG神经元和卫星胶质细胞。U 0126抑制轴突切断诱导的自切断行为，并逆转p-ERK和BDNF的增加。鞘内应用神经生长因子（NGF）可诱导p-ERK和BDNF标记细胞（主要是小神经元）数量增加，应用抗NGF可诱导部分中、大直径DRG神经元p-ERK和BDNF表达增加。MAPK在初级传入的激活可能发生在不同群体的DRG神经元外周炎症和轴突切断术后，分别通过靶源性NGF的改变。这些变化，包括BDNF表达的变化，可能参与了初级传入神经元的病理生理变化。
To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor ( BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and sciatic nerve transection. Peripheral inflammation induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase A-containing small-to-medium-diameter DRG neurons. The treatment of the mitogen-activated protein kinase ( MAPK) kinase 1/2 inhibitor U0126 reversed the pain hypersensitivity and the increase in phosphorylated-ERK (p-ERK) and BDNF in DRG neurons induced by complete Freund's adjuvant. On the other hand, axotomy induced the activation of ERK mainly in medium- and large-sized DRG neurons and in satellite glial cells. U0126 suppressed the axotomy-induced autotomy behavior and reversed the increase in p-ERK and BDNF. The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK- and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons. The activation of MAPK in the primary afferents may occur in different populations of DRG neurons after peripheral inflammation and axotomy, respectively, through alterations in the target-derived NGF. These changes, including the changes in BDNF expression, might be involved in the pathophysiological changes in primary afferent neurons.