学习和记忆的恢复与染色质重塑有关
Andre Fischer1, Farahnaz Sananbenesi, Xinyu Wang
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA. andre.fischer@mpi-mail.mpg.de
Nature
|May 1, 2007
概括
在神经退行性疾病的小鼠模型中,环境丰富和胰岛素脱乙酶抑制剂可以恢复学习和长期记忆,即使在大脑损伤后也是如此. 这表明痴呆症的潜在治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 神经退行性疾病会影响学习和记忆,导致痴呆.
- 在临床前研究中,恢复认知功能和记忆访问是至关重要的.
研究的目的:
- 调查环境丰富是否可以在神经退行症小鼠模型中逆转学习和记忆缺陷.
- 探索分子机制,包括染色质修饰,基础的记忆恢复.
- 评估基因素脱乙酶抑制剂的治疗潜力.
主要方法:
- 使用了具有受控神经元损失的小鼠模型.
- 实施的环境丰富协议.
- 分析了染色质修饰,特别是基因素乙化.
- 已使用的希斯脱乙酶抑制剂.
- 评估学习行为和长期记忆回忆.
主要成果:
- 环境丰富恢复了学习行为和记忆访问,尽管大脑显著缩.
- 丰富与增加的基因尾乙化相关.
- 素脱乙酶的抑制促进了树突发芽和突触数量的增加.
- 抑制胰岛素脱乙酶也恢复了学习和记忆.
结论:
- 环境丰富可以恢复神经退行性疾病中的认知功能和记忆访问.
- 素乙化在这个恢复过程中起着关键作用.
- 基斯脱乙酶抑制剂代表了神经退行性疾病与认知障碍的有希望的治疗策略,可能有助于痴呆症患者的长期记忆恢复.
相关概念视频
Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Duplication of Chromatin Structure
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...


