Inhibiting geranylgeranyltransferase I activity decreases spine density in central nervous system
Inhibiting geranylgeranyltransferase I activity decreases spine density in central nervous system
复制标题
抑制香叶基香叶基转移酶 I 活性可降低中枢神经系统的脊柱密度
DOI：
10.1002/hipo.22379
复制
发表时间：
2015-03
期刊：
影响因子：
3.5
通讯作者：
Zhou Xiuping
中科院分区：
文献类型：
--
作者：
Yuan Maochun;Gao Shangfeng;Sun Chengdong;Chen Long;Shi Qiong;Hu Jinxia;Yu Rutong;Zhou Xiuping
牛儿基牛儿基转移酶I（GGT）是一种异戊烯基转移酶，负责Rac、Rho和Cdc 42等Rho GTP酶的翻译后脂化，这些酶在神经元突触发生中起重要作用。我们以前证明，GGT促进培养的海马神经元和小脑切片的树突形态发生。我们在此报告，抑制GGT活性可降低小鼠体内棘密度以及学习和记忆能力的基础和活性依赖性变化。我们发现，在培养的海马神经元中，特异性GGT抑制剂GGTi-2147处理消除了KCl或荷包牡丹碱诱导的树突棘密度增加。侧脑室注射GGTi-2147可降低GGT活性和Rac的膜结合，并降低小鼠海马、额叶皮质和小脑中树突棘的密度。GGTi-2147给药也损害了小鼠的学习和记忆能力。更重要的是，暴露于环境富集（EE）的小鼠表现出脊柱密度增加以及学习和记忆能力，这一点在GGTi-2147给药后显著逆转。这些数据表明，在体外和体内，抑制GGT活性可防止中枢神经系统中棘密度的基础和活性依赖性变化。操纵GGT活性可能是治疗神经发育障碍如自闭症、抑郁症和精神分裂症的一种有前途的策略。© 2014 Wiley Periodicals，Inc.
Geranylgeranyltransferase I (GGT), a protein prenyltransferase, is responsible for the posttranslational lipidation of Rho GTPases, such as Rac, Rho and Cdc42, all of which play an important role in neuronal synaptogenesis. We previously demonstrated that GGT promotes dendritic morphogenesis in cultured hippocampal neurons and cerebellar slices. We report here that inhibiting GGT activity decreases basal‐ and activity‐dependent changes in spine density as well as in learning and memory ability of mice in vivo. We found that KCl‐ or bicuculline‐induced dendritic spine density increases was abolished by specific GGT inhibitor GGTi‐2147 treatment in cultured hippocampal neurons. GGTi‐2147 lateral ventricular injection reduced GGT activity and membrane association of Rac and decreased the density of dendritic spines in the mouse hippocampus, frontal cortex and cerebellum. GGTi‐2147 administration also impaired learning and memory ability of mice. More importantly, mice exposed to environmental enrichment (EE) showed increased spine density and learning and memory ability, which were significantly reversed by GGTi‐2147 administration. These data demonstrate that inhibiting GGT activity prevents both basal‐ and activity‐dependent changes in spine density in central nervous system both in vitro and in vivo. Manipulating GGT activity may be a promising strategy for the therapies of neurodevelopmental disorders, such as autism, depression, and schizophrenia. © 2014 Wiley Periodicals, Inc.
登录
查看更多内容
香叶基香叶基转移酶 I 对于小脑浦肯野细胞的树突发育至关重要。
影响因子：
3.6
作者：
Wu, Kong-Yan;Zhou, Xiu-Ping;Luo, Zhen-Ge
通讯作者：
Luo, Zhen-Ge
DOI：
10.1007/978-94-015-9460-8_17
发表时间：
2000
期刊：
--
影响因子：
--
作者：
Hai Li;Zhenbiao Yang
通讯作者：
Hai Li;Zhenbiao Yang
影响因子：
5.7
作者：
L. Aelst;H. Cline
通讯作者：
L. Aelst;H. Cline
影响因子：
4.7
作者：
Li, Zhengwei;Sun, Chengdong;Zhou, Xiuping
通讯作者：
Zhou, Xiuping
DOI：
10.1523/jneurosci.2456-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boersma MC;Dresselhaus EC;De Biase LM;Mihalas AB;Bergles DE;Meffert MK
通讯作者：
Meffert MK