Zoubaa S, Konrad R, Piontek G, Schlegel J
Institute of Pathology, Division of Neuropathology, Technical University, Ismaninger Strasse 22, D-81675 Munich, Germany.
Neurosci Lett. 2010 Jun 7;476(3):113-8. doi: 10.1016/j.neulet.2010.01.070. Epub 2010 Feb 4.
Amphetamine analogs are known to induce not only neurotoxicity at serotonergic axon terminals but also neocortical neuronal degeneration. However, a much less studied aspect involves the impact of amphetamine exposure on neuronal development. The present study investigated whether pretreatment of PC12 cells with dioxyamphetamine (DA) alters differentiation of PC12 cells by NGF and, if so, which components of the Ras/Raf/MEK/ERK pathway known to be involved in the differentiation response to NGF are particularly affected. Though exposure of PC12 cells to DA 1h prior to NGF treatment resulted in apopotosis, several PC12 cells survived. However, neurite outgrowth of these NGF-responsive cells was repressed. Immunoblots of whole cell extracts revealed a strong induction rather than inhibition of ERK phosphorylation up to 48h after DA/NGF treatment. Our results indicate that NGF-mediated neurite outgrowth was inhibited by pretreatment with DA, and this blockage of NGF-induced neuritogenesis was not due to an inhibition of ERK phosphorylation.
苯丙胺类似物不仅已知会在5-羟色胺能轴突终末诱导神经毒性，还会导致新皮质神经元变性。然而，一个研究较少的方面涉及苯丙胺暴露对神经元发育的影响。本研究调查了用二氧苯丙胺（DA）预处理PC12细胞是否会改变PC12细胞由神经生长因子（NGF）诱导的分化，如果是这样，已知参与对NGF分化反应的Ras/Raf/MEK/ERK途径的哪些成分会受到特别影响。尽管在NGF处理前1小时将PC12细胞暴露于DA会导致细胞凋亡，但仍有一些PC12细胞存活。然而，这些对NGF有反应细胞的神经突生长受到抑制。全细胞提取物的免疫印迹显示，在DA/NGF处理后长达48小时，ERK磷酸化有强烈的诱导而非抑制。我们的结果表明，用DA预处理会抑制NGF介导的神经突生长，并且这种对NGF诱导的神经突形成的阻断不是由于ERK磷酸化的抑制。
