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突变FUS诱导海马体中的染色质重组,并改变记忆过程

Laura Tzeplaeff¹, Jonathan Seguin², Stéphanie Le Gras³

¹Université de Strasbourg, Laboratoire de Neuroscience Cognitives et Adaptatives (LNCA), Strasbourg, France; CNRS, UMR 7364, Strasbourg 67000, France; Université de Strasbourg, INSERM, UMR-S1118, Strasbourg, France.

Progress in neurobiology

|June 16, 2023

概括

突变小鼠海马体中核FUS积累具有悖论性的影响空间记忆和染色素. 这种表观遗传失调为FUS相关的神经退行性疾病提供了新的治疗点.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

核化在肉瘤 (FUS) 蛋白质的细胞质错位与肌缩侧面硬化症 (ALS) 和前性痴呆症 (FTD) 有关.
之前的研究观察到异合体Fus小鼠的前皮层和脊髓中FUS积累,但其对海马的影响尚不清楚.

研究的目的:

研究将FUS错位化与海马功能和记忆形成联系在一起的机制.
描述FUS突变对海马内表观遗传调节和神经元功能的影响.

主要方法:

多原子分析以确定海马体中的FUS结合标.
在海马神经元中的染色体分解评估.
在空间训练后进行转录形状分析.
空间记忆精度的行为测试.
树突性脊柱密度分析.

主要成果:

矛盾的是,Fus^∆NLS/+小鼠在海马体中呈现出核FUS积累.
发现FUS结合了参与RNA代谢,转录和染色质组织的基因.
海马神经元在高度表达的基因和对空间训练的异常转录组反应上显示了染色质分解.
突变小鼠显示空间记忆精度受损,树突脊柱密度降低.

结论:

突变的FUS破坏了海马神经元中染色质景观的表观遗传调节.
这些表观遗传变化可能有助于FTD和ALS的发病.
需要对FUS相关疾病的神经现象类型进行进一步的研究,并有可能进行表观遗传药物治疗.

关键词:

在ALS/FTD中,这就是FUS FUS.在海马体内,海马体基质子的修改基质子的修改神经元染色素是神经元中的一种染色体.空间记忆是一种空间记忆.

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