首页> 外文期刊>The European Journal of Neuroscience >Ablation of serum response factor in dopaminergic neurons exacerbates susceptibility towards MPTP-induced oxidative stress
【24h】

Ablation of serum response factor in dopaminergic neurons exacerbates susceptibility towards MPTP-induced oxidative stress

机译:多巴胺能神经元中血清反应因子的消融加剧了对MPTP诱导的氧化应激的敏感性

获取原文
获取原文并翻译 | 示例
           

摘要

The high susceptibility of dopaminergic (DA) neurons to cellular stress is regarded as a primary cause of Parkinson's disease. Here we investigate the role of the serum response factor (SRF), an important regulator of anti-apoptotic responses, for the survival of DA neurons in mice. We show that loss of SRF in DA neurons does not affect their viability and does not influence dopamine-dependent behaviors. However, ablation of SRF causes exacerbated sensitivity to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP), leading to significantly greater loss of DA neurons in the substantia nigra, compared with DA neurons located in the ventral tegmental area. In addition, loss of SRF decreases levels of the anti-apoptotic proteins brain-derived neurotrophic factor (BDNF) and Bcl-2, a plausible underlying cause of increased sensitivity to oxidative stress. These observations support the notion that dysfunction of the SRF-activating mitogen-associated kinase pathway may be part of Parkinson's disease etiology.
机译:多巴胺能(DA)神经元对细胞应激的高度敏感性被认为是帕金森氏病的主要原因。在这里,我们研究了血清反应因子(SRF)(抗凋亡反应的重要调节剂)对小鼠DA神经元存活的作用。我们表明,DA神经元中SRF的丢失不会影响其生存力,也不会影响多巴胺依赖性行为。然而,SRF的消融导致对1-甲基4-苯基1,2,3,6-四氢吡啶(MPTP)的敏感性增强,与位于腹侧被盖区的DA神经元相比,黑质中DA神经元的损失明显增加。区。此外,SRF的丧失降低了脑源性神经营养因子(BDNF)和Bcl-2的抗凋亡蛋白水平,Bcl-2可能是对氧化应激敏感的潜在原因。这些观察结果支持以下观点:SRF激活丝裂原相关激酶途径的功能障碍可能是帕金森氏病病因的一部分。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号