Aldolase C-positive cerebellar Purkinje cells are resistant to delayed death after cerebral trauma and AMPA-mediated excitotoxicity
Aldolase C-positive cerebellar Purkinje cells are resistant to delayed death after cerebral trauma and AMPA-mediated excitotoxicity
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DOI：
10.1111/j.1460-9568.2007.05708.x
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Weber, John T.
中科院分区：
文献类型：
--
作者：
Slemmer, Jennifer E.;Haasdijk, Elize D.;Weber, John T.
小脑已被证明是脆弱的全面缺血性损伤的浦肯野细胞（PC）的严格控制区，缺乏醛缩酶C，糖酵解的关键酶。在这里，我们研究了是否醛缩酶C阴性的PC更容易在体内脑创伤后死亡，以及这种死亡是否是由兴奋性毒性[α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）介导的]体外手段介导的。对小鼠进行受控的皮质撞击，或保持未受伤，并在损伤后6小时、24小时或7天处死。小脑切片（脑损伤部位的同侧和对侧）针对醛缩酶C和钙结合蛋白（PC的标记物）染色。存活的钙结合蛋白阳性PC的数量在损伤后24小时和7天显著减少，而存活的醛缩酶C阳性PC的百分比在这些时间点显著增加。此外，我们进行鼠小脑培养AMPA（30 μ m，20分钟），这杀死了显着数量的PC在24小时后处理。用醛缩酶C siRNA转染后，丢失了类似数量的PC，并且在用AMPA处理的转染培养物中，这种效应加剧。本研究的结果表明，醛缩酶C提供显着的神经保护PC创伤和兴奋性中毒后。
The cerebellum has been shown to be vulnerable to global ischemic damage in tightly controlled zones of Purkinje cells (PCs) that lack aldolase C, an enzyme critical for glycolysis. Here, we investigated whether aldolase C-negative PCs were more likely to die after cerebral trauma in vivo, and whether this death was mediated by excitotoxic [alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated] means in vitro. Mice were subjected to controlled cortical impact, or remained uninjured, and were killed at 6 h, 24 h or 7 days after injury. Cerebellar sections (both ipsilateral and contralateral to the site of cerebral injury) were stained against aldolase C and calbindin (a marker of PCs). The number of viable, calbindin-positive PCs decreased significantly at 24 h and 7 days after injury, and the percentage of surviving, aldolase C-positive PCs significantly increased at those time-points. In addition, we subjected murine cerebellar cultures to AMPA (30 mu m, 20 min), which killed a significant number of PCs at 24 h post-treatment. A similar number of PCs was lost after transfection with aldolase C siRNA, and this effect was exacerbated in transfected cultures treated with AMPA. The results from the present study indicate that aldolase C provides marked neuroprotection to PCs after trauma and excitotoxicity.