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首页> 外文期刊>The European Journal of Neuroscience >Differential contributions of de novo and maintenance DNA methyltransferases to object memory processing in the rat hippocampus and perirhinal cortex - a double dissociation
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Differential contributions of de novo and maintenance DNA methyltransferases to object memory processing in the rat hippocampus and perirhinal cortex - a double dissociation

机译：从头和维持DNA甲基转移酶对大鼠海马和周围神经皮层对象记忆处理的不同贡献-双重解离

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摘要

Epigenetic mechanisms are increasingly acknowledged as major players in memory formation. Specifically, DNA methylation is necessary for the formation of long-term memory in various brain regions, including the hippocampus (HPC); however, its role in the perirhinal cortex (PRh), a structure critical for object memory, has not been characterized. Moreover, the mnemonic effects of selective DNA methyltransferase (DNMT) inhibition have not yet been investigated systematically, despite distinct roles for de novo (DNMT3a, 3b) and maintenance (DNMT1) methyltransferases. Consequently, we assessed the effects of various DNMT inhibitors within the HPC and PRh of rats using the object-in-place paradigm, which requires both brain regions. The non-nucleoside DNA methyltransferase inhibitor RG-108 impaired long-term object-in-place memory in both regions. Furthermore, intracranial administration of Accell short-interference RNA sequences to inhibit the expression of individual DNMTs implicated DNMT3a and DNMT1 in the HPC and PRh effects, respectively. mRNA expression analyses revealed a complementary pattern of results, as only de novo DNMT3a and DNMT3b mRNA was upregulated in the HPC (dentate gyrus) following object-in-place learning, whereas DNMT1 mRNA was selectively upregulated in the PRh. These results reinforce the established functional double dissociation between the HPC and PRh and imply the operation of different epigenetic mechanisms in brain regions dedicated to long-term memory processing for different types of information.
机译：表观遗传机制日益被认为是记忆形成的主要参与者。具体来说，DNA甲基化对于在包括海马（HPC）在内的各种大脑区域形成长期记忆是必不可少的。但是，其在周围神经皮质（PRh）中的作用尚未确定，PRh是一种对对象记忆至关重要的结构。此外，尽管从头（DNMT3a，3b）和维持（DNMT1）甲基转移酶起着不同的作用，但是选择性DNA甲基转移酶（DNMT）抑制的记忆作用尚未得到系统的研究。因此，我们使用需要两个大脑区域的原位对象范例评估了大鼠HPC和PRh中各种DNMT抑制剂的作用。非核苷DNA甲基转移酶抑制剂RG-108损害了两个区域的长期就地存储。此外，颅内给予Accell短干扰RNA序列以抑制单个DNMT的表达，分别涉及HPC和PRh效应中的DNMT3a和DNMT1。 mRNA表达分析揭示了结果的互补模式，因为在原位学习后，只有从头DNMT3a和DNMT3b mRNA在HPC（齿状回）中被上调，而DNMT1 mRNA在PRh中被选择性地上调。这些结果加强了HPC和PRh之间已建立的功能性双重解离，并暗示着大脑区域中不同表观遗传机制的运作，这些机制专门用于对不同类型的信息进行长期记忆处理。

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