Central administration of a caspase inhibitor impairs shuttle-box performance in rats
Central administration of a caspase inhibitor impairs shuttle-box performance in rats
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DOI：
10.1016/j.neuroscience.2005.08.010
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Gulyaeva, NV
中科院分区：
文献类型：
--
作者：
Stepanichev, MY;Kudryashova, IV;Gulyaeva, NV
最近的研究表明 caspase-3 介导的机制对于神经元可塑性至关重要。 N-苄基-氧羰基-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-氟甲基酮 (z-DEVD-fmk) 是一种对 caspase-3 具有显着特异性的 caspase 抑制剂，已被证明可以阻断海马切片中的长时程增强。研究表明，向大鼠海马内注射 caspase-3 抑制剂会显着损害水迷宫中的空间记忆。目前的工作旨在研究 i.c.v.给予 caspase-3 抑制剂 z-DEVD-fmk 会损害大鼠与特定记忆形式相关的其他任务的学习。大鼠接受剂量为 3 nmol 的 z-DEVD-fmk 或 N-苄氧基羰基-Phe-Ala-氟甲基酮 (z-FA-fmk)（“对照”肽）双侧注射。在主动回避（穿梭箱）学习的一些试验中，给予 z-DEVD-fmk 显着减少了回避反应的数量，而 z-FA-fmk 与完整大鼠相比没有效果。然而，在整个疗程中只发现半胱天冬酶抑制剂有轻微的作用。 z-DEVD-fmk 损害了双向主动回避表现的一些重要组成部分的发展，例如逃避反应、条件性恐惧反应和试验间交叉。对参与主动回避学习的大鼠大脑区域中 caspase-3 活性的测量显示，额顶叶皮层中表达最多的 z-DEVD-fmk 相关酶活性抑制（约 30%）。类似的效果在海马体中接近显着，但在所研究的其他大脑结构中则不然。在小脑神经元的原代培养物中，z-DEVD-fmk (2-50 mu M) 抑制 caspase-3 活性达 60-87%。我们认为，对大鼠中央给予 z-DEVD-fmk 造成的 caspase-3 的中度抑制可能会损害主动回避学习。考虑到先前有关神经元 caspase-3 参与神经可塑性现象的数据，我们假设该酶可能对于选定的学习形式很重要。 (c) 2005 年由 Elsevier Ltd 代表 IBRO 出版。
Recent studies suggest that caspase-3-medlated mechanisms are essential for neuronal plasticity. N-benzyl-oxycarbonyl-Asp(OMe)-Glu(OMe)-Val- Asp(OMe)-fluoromethyl ketone (z-DEVD-fmk), a caspase inhibitor with predominant specificity toward caspase-3, has been shown to block long-term potentiation in hippocampal slices. Intrahippocampal infusion of a caspase-3 inhibitor to rats has been shown to significantly impair spatial memory in the water maze. The present work was designed to study whether i.c.v. administration of a caspase-3 inhibitor z-DEVD-fmk impairs learning in other tasks related to specific forms of memory in rats. The rats received bilateral injections of z-DEVD-fmk or N-benzyloxycarbonyl-Phe-Ala-fluoromethyl ketone (z-FA-fmk) ("control" peptide) at a dose of 3 nmol. Administration of z-DEVD-fmk significantly decreased the number of avoidance reactions in some blocks of trials in the active avoidance (shuttle box) learning, while z-FA-fmk had no effect as compared with intact rats. However, only a slight effect of the caspase inhibitor across the session was found. z-DEVD-fmk impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings. Measurement of caspase-3 activity in rat brain regions involved in active avoidance learning revealed most expressed z-DEVD-fmk-related inhibition of the enzyme activity (about 30%) in the fronto-parietal cortex. A similar effect was close to significant in the hippocampus, but not in the other cerebral structures studied. In primary cultures of cerebellar neurons z-DEVD-fmk (2-50 mu M) inhibited caspase-3 activity by 60-87%. We suggest that moderate inhibition of caspase-3 resulting from the central administration of z-DEVD-fmk to rats may impair active avoidance learning. Taking into account previous data on the involvement of neuronal caspase-3 in neuroplasticity phenomena we assume that the enzyme may be important for selected forms of learning. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.