认知过程中的表观遗传学机制

Epigenetic mechanism in cognitive function

该文首先对什么是表观遗传学及其细胞学基础作了介绍,随后,对认知功能中的表观遗传学机制的研究进展进行了综述。各方面研究一致证明,在海马、皮层及其它脑区发生的表观遗传学改变如组蛋白的乙酰化、甲基化、磷酸化、泛素化、多聚(ADP-核糖)聚合酶化和DNA甲基化可稳定地改变动物的行为,包括学习、记忆、突触可塑性、抑郁、药物成瘾等。不过,在长记忆和突触可塑形成过程中,需要CREB结合蛋白CP的存在并与CREB相结合,最后导致与记忆及突触可塑性有关的基因(如Zif/268,Greb,Bdnf,Reelin等)的转录和表达。相反,在衰老和神经退行性疾病脑内出现表观遗传学的异常改变,如组蛋白低甲基化、组蛋白去乙酰化转移酶活性增加等。鉴于上述,对神经退行性疾病的治疗策略是:提高组蛋白乙酰化和组蛋白、DNA甲基化,应用HDAC抑制剂及RNA干扰(RNAi)可有效地改善记忆,提高突触可塑性和阻遏学习记忆下降。

The definition of epigenetics and its cellular basis are introduced firstly in the paper. Then, the research progress on the relationship between cognition and epigenetic changes is re-viewed in detail. In conclusion, epigenetic modifications occur-ring in hippocampus, cortex and other brain areas such as methy-lation , phosphorylation , ubiquitination , poly （ ADP-ribos ） poly-merases and DNA methylation may certainly change animal be-haviors including learning, memory, synaptic plasticity, depres-sion, drug abuse and so on. Long-term memory and long-term potentiation（ LTP） , activation of AMPK-ERK signal transduction path-way and activation of key gene regulated by CREB-ABP transcriptional complex as well as transcription and expression of memory and synaptic plasticity related genes （ Zif/268, Creb, Bdnf, reelin ） are required. In contrast, epigenetic abnormal changes such as histone and DNA hypomethylation and increase＆amp;nbsp;of HDAC activity are observed in brains of aging and neurodegen-erative diseases. Therefore, the main epigenetic treatments for cognitive impairments are increasing histone and DNA methyla-tion, using HDAC inhibitors and RNA interference （ RNAi） to promote formation of long term memory and long term potentia-tion, block learning and memory decline.