Mustafin R N
Bashkir State Medical University, Ufa, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2024 Sep;28(5):476-486. doi: 10.18699/vjgb-24-54.
The review describes the hypothesis that the drivers of epigenetic regulation in memory formation are transposable elements that influence the expression of specific genes in the brain. The hypothesis is confirmed by research into transposon activation in neuronal stem cells during neuronal differentiation. These changes occur in the hippocampus dentate gyrus, where a pronounced activity of transposons and their insertion near neuron-specific genes have been detected. In experiments on changing the activity of histone acetyltransferase and inhibition of DNA methyltransferase and reverse transcriptase, the involvement of epigenetic factors and retroelements in the mechanisms of memory formation has been shown. Also, a number of studies on different animals have revealed the preservation of long-term memory without the participation of synaptic plasticity. The data obtained suggest that transposons, which are genome sensors highly sensitive to various environmental and internal influences, form memory at the nuclear coding level. Therefore, long-term memory is preserved after elimination of synaptic connections. This is confirmed by the fact that the proteins involved in memory formation, including the transfer of genetic information through synapses between neurons (Arc protein), originate from transposons. Long non-coding RNAs and microRNAs also originate from transposons; their role in memory consolidation has been described. Pathological activation of transposable elements is a likely cause of neurodegenerative diseases with memory impairment. Analysis of the scientific literature allowed us to identify changes in the expression of 40 microRNAs derived from transposons in Alzheimer's disease. For 24 of these microRNAs, the mechanisms of regulation of genes involved in the functioning of the brain have been described. It has been suggested that the microRNAs we identified could become potential tools for regulating transposon activity in the brain in order to improve memory.
这篇综述描述了一种假说，即记忆形成过程中表观遗传调控的驱动因素是转座元件，它们会影响大脑中特定基因的表达。对神经元分化过程中神经元干细胞中转座子激活的研究证实了这一假说。这些变化发生在海马齿状回，在那里已检测到转座子的显著活性及其在神经元特异性基因附近的插入。在改变组蛋白乙酰转移酶活性以及抑制DNA甲基转移酶和逆转录酶的实验中，已表明表观遗传因子和逆转录元件参与了记忆形成机制。此外，一些针对不同动物的研究揭示了在没有突触可塑性参与的情况下长期记忆的保存。所获得的数据表明，作为对各种环境和内部影响高度敏感的基因组传感器的转座子，在核编码水平上形成记忆。因此，在消除突触连接后长期记忆得以保留。这一点得到了以下事实的证实：参与记忆形成的蛋白质，包括通过神经元之间的突触传递遗传信息的蛋白质（Arc蛋白），都源自转座子。长链非编码RNA和微小RNA也源自转座子；它们在记忆巩固中的作用已有描述。转座元件的病理性激活可能是导致伴有记忆障碍的神经退行性疾病的原因。对科学文献的分析使我们能够确定在阿尔茨海默病中源自转座子的40种微小RNA的表达变化。对于其中24种微小RNA，已描述了其参与大脑功能的相关基因的调控机制。有人提出，我们鉴定出的这些微小RNA可能成为调节大脑中转座子活性以改善记忆的潜在工具。
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