Sirtuin 1 overexpression mice show a reference memory deficit, but not neuroprotection
Sirtuin 1 overexpression mice show a reference memory deficit, but not neuroprotection
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DOI：
10.1016/j.bbrc.2009.07.119
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发表时间：
2009-10-02
影响因子：
3.1
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Kakefuda, Kenichi;Fujita, Yasunori;Hara, Hideaki
Sirtuin 1（SIRT 1）是与酵母沉默信息调节因子2（Sir2）最接近的哺乳动物同源物，并且在寿命调节中起作用。据报道，SIRT1也与神经退行性疾病有关。然而，有有限的研究报告之间的关系SIRT1和神经退行性疾病使用体内转基因（Tg）的方法。在本研究中，我们产生了神经元特异性烯醇化酶（NSE）SIRT1 Tg小鼠，在神经元中过表达人SIRT1。我们研究了SIRT1过表达可能的神经保护作用，并将其与野生型（WT）小鼠的脑功能进行了比较。过表达SIRT1对缺血或1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的神经元损伤无保护作用。然而，SIRT1 Tg小鼠表现出参考记忆缺陷。这些结果表明，SIRT1的过度表达可能会导致小鼠记忆障碍，但没有神经保护作用。(C)2009 Elsevier Inc. All rights reserved.
Sirtuin 1 (SIRT1) is the closest mammalian homologue of yeast silent information regulator 2 (Sir2) and has a role in lifespan modulation. Reportedly, SIRT1 is also linked to neurodegenerative diseases. However, there are limited studies that report the relation between SIRT1 and neurodegenerative diseases using in vivo transgenic (Tg) methods. In the present study, we generated neuron-specific enolase (NSE) SIRT1 Tg mice that overexpress human SIRT1 in neurons. We examined possible neuroprotective effects of SIRT1 overexpression and compared their higher brain functions with those of wild-type (WT) mice. Overexpression of SIRT1 did not have any neuroprotective effects against the neuronal damage induced by ischemia or 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). However, SIRT1 Tg mice exhibited a reference memory deficit. These findings suggest that an excessive expression of SIRT1 might induce the memory deficit in mice, but not neuroprotective effects. (C) 2009 Elsevier Inc. All rights reserved.