Kakefuda Kenichi, Fujita Yasunori, Oyagi Atsushi, Hyakkoku Kana, Kojima Toshio, Umemura Ken, Tsuruma Kazuhiro, Shimazawa Masamitsu, Ito Masafumi, Nozawa Yoshinori, Hara Hideaki
Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan.
Biochem Biophys Res Commun. 2009 Oct 2;387(4):784-8. doi: 10.1016/j.bbrc.2009.07.119. Epub 2009 Jul 28.
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.
沉默信息调节因子1（SIRT1）是酵母沉默信息调节因子2（Sir2）在哺乳动物中最接近的同源物，在寿命调节中发挥作用。据报道，SIRT1也与神经退行性疾病有关。然而，使用体内转基因（Tg）方法报道SIRT1与神经退行性疾病之间关系的研究有限。在本研究中，我们生成了神经元特异性烯醇化酶（NSE）SIRT1转基因小鼠，其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，并将其高级脑功能与野生型（WT）小鼠进行比较。SIRT1的过表达对缺血或1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的神经元损伤没有任何神经保护作用。然而，SIRT1转基因小鼠表现出参考记忆缺陷。这些发现表明，SIRT1的过度表达可能会导致小鼠记忆缺陷，但没有神经保护作用。
