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17β-雌二醇对 NSC-34 细胞和脊髓中海马乙酰胆碱转移酶表达的调控。

Regulation of choline acetyltransferase expression by 17 β-oestradiol in NSC-34 cells and in the spinal cord.

机构信息

Institute of Neuroanatomy, RWTH Aachen University, Aachen, Germany.

出版信息

J Neuroendocrinol. 2011 Sep;23(9):839-48. doi: 10.1111/j.1365-2826.2011.02192.x.

Abstract

Motoneurones located in the ventral horn of the spinal cord conciliate cholinergic innervation of skeletal muscles. These neurones appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis. The dysfunction of motoneurones is typically accompanied by alterations of cholinergic metabolism and signalling, as demonstrated by a decrease in choline acetyltransferase (ChAT) expression. 17 β-Oestradiol (E(2)) is generally accepted as neuroprotective factor in the brain under acute toxic and neurodegenerative conditions and also appears to exert a protective role for motoneurones. In the present study, we attempted to analyse the role of E(2) signalling on ChAT expression in the motoneurone-like cell line NSC-34 and in vivo. In a first step, we demonstrated the presence of oestrogen receptor α and β in NSC-34 cells, as well as in the cervical and lumbar parts, of the male mouse spinal cord. Subsequently, we investigated the effect of E(2) treatment on ChAT expression. The application of E(2) significantly increased the transcription of ChAT in NSC-34 cells and in the cervical but not lumbar part of the spinal cord. Our results indicate that E(2) can influence the cholinergic system by increasing ChAT expression in the mouse spinal cord. This mechanism might support motoneurones, in addition to survival-promoting mechanisms, in the temporal balance toxic or neurodegenerative challenges.

摘要

位于脊髓腹角的运动神经元协调骨骼肌的胆碱能神经支配。这些神经元似乎在神经退行性疾病(如肌萎缩侧索硬化症)中受到极大影响。运动神经元的功能障碍通常伴随着胆碱能代谢和信号的改变,表现为胆碱乙酰转移酶(ChAT)表达的减少。17β-雌二醇(E(2))通常被认为是急性毒性和神经退行性条件下大脑中的神经保护因子,并且似乎对运动神经元也发挥保护作用。在本研究中,我们试图分析 E(2)信号对运动神经元样细胞系 NSC-34 和体内 ChAT 表达的作用。在第一步中,我们证明了 NSC-34 细胞以及雄性小鼠脊髓的颈段和腰段存在雌激素受体α和β。随后,我们研究了 E(2)处理对 ChAT 表达的影响。E(2)的应用显著增加了 NSC-34 细胞和脊髓颈段 ChAT 的转录,但不增加脊髓腰段的 ChAT 转录。我们的结果表明,E(2)可以通过增加小鼠脊髓中的 ChAT 表达来影响胆碱能系统。这种机制可能除了生存促进机制外,还可以在时间上平衡毒性或神经退行性挑战对运动神经元的影响。

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