Improvement of Learning and Memory by Elevating Brain D-Aspartate in a Mouse Model of Fragile X Syndrome.
Improvement of Learning and Memory by Elevating Brain D-Aspartate in a Mouse Model of Fragile X Syndrome.
复制标题
DOI：
10.1007/s12035-023-03438-0
复制
发表时间：
2023-11
影响因子：
5.1
通讯作者：
Zhao, Ming-Gao
中科院分区：
文献类型：
--
作者：
Li, Yu-Jiao;Zhang, Kun;Sun, Ting;Guo, Yan-Yan;Yang, Qi;Liu, Shui-Bing;Wu, Yu-Mei;Zhao, Ming-Gao
脆性X综合征（FXS）是一种遗传性人类智力低下，由Fmr 1基因中CGG重复序列的扩增引起，导致脆性X智力低下蛋白（FMRP）的丢失。据报道，N-甲基-D-天冬氨酸受体（NMDAR）介导的易化长时程增强（LTP）和恐惧记忆在Fmr 1基因敲除（KO）小鼠中受损。在这项研究中，生物学，药理学和电生理技术进行，以确定D-天冬氨酸（D-Asp），一个NMDAR的调节剂，其代谢酶D-天冬氨酸氧化酶（DDO）在Fmr 1基因敲除小鼠的作用。内侧前额叶皮质（mPFC）中D-Asp水平降低，但其代谢酶DDO水平升高。电生理记录表明，口服D-Asp恢复了Fmr 1 KO小鼠mPFC中的LTP诱导。此外，长期口服D-Asp可逆转Fmr 1 KO小鼠的认知和运动协调行为缺陷。D-Asp的治疗作用部分是通过调节NMDARs和mGluR 5/mTOR/4 E-BP信号通路发挥作用。结论：补充D-Asp可改善Fmr 1基因敲除小鼠的突触可塑性和行为，为FXS的治疗提供了一种新的策略。
Fragile X syndrome (FXS) is an inherited human mental retardation that arises from expansion of a CGG repeat in the Fmr1 gene, causing loss of the fragile X mental retardation protein (FMRP). It is reported that N-methyl-D-aspartate receptor (NMDAR)-mediated facilitation of long-term potentiation (LTP) and fear memory are impaired in Fmr1 knockout (KO) mice. In this study, biological, pharmacological, and electrophysiological techniques were performed to determine the roles of D-aspartate (D-Asp), a modulator of NMDAR, and its metabolizing enzyme D-aspartate oxidase (DDO) in Fmr1 KO mice. Levels of D-Asp were decreased in the medial prefrontal cortex (mPFC); however, the levels of its metabolizing enzyme DDO were increased. Electrophysiological recordings indicated that oral drinking of D-Asp recovered LTP induction in mPFC from Fmr1 KO mice. Moreover, chronic oral administration of D-Asp reversed behavioral deficits of cognition and locomotor coordination in Fmr1 KO mice. The therapeutic action of D-Asp was partially through regulating functions of NMDARs and mGluR5/mTOR/4E-BP signaling pathways. In conclusion, supplement of D-Asp may benefit for synaptic plasticity and behaviors in Fmr1 KO mice and offer a potential therapeutic strategy for FXS.
登录
查看更多内容
影响因子：
34.7
作者：
Lisman, John;Yasuda, Ryohei;Raghavachari, Sridhar
通讯作者：
Raghavachari, Sridhar
DOI：
10.1007/978-1-61779-331-8_16
发表时间：
2012-01-01
期刊：
UNNATURAL AMINO ACIDS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Fisher, George H.;Tsesarskaia, Mara
通讯作者：
Tsesarskaia, Mara
DOI：
10.1073/pnas.1013855108
发表时间：
2011-02-08
影响因子：
11.1
作者：
Krueger, Dilja D.;Osterweil, Emily K.;Bear, Mark F.
通讯作者：
Bear, Mark F.
影响因子：
3.5
作者：
Li, JX;Pelletier, MR;Carlen, PL
通讯作者：
Carlen, PL
影响因子：
5.3
作者：
Pfeiffer, Brad E.;Huber, Kimberly M.
通讯作者：
Huber, Kimberly M.