Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function.
Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function.
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DOI：
10.1016/j.isci.2023.107566
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发表时间：
2023-09-15
期刊：
影响因子：
5.8
通讯作者：
Cahill, Michael E.
中科院分区：
文献类型：
--
作者：
Bjornson, Kathryn J.;Vanderplow, Amanda M.;Yang, Yezi;Anderson, Danielle R.;Kermath, Bailey A.;Cahill, Michael E.
反复压力对认知障碍的影响被认为至少部分是通过降低大脑中对正确学习和记忆至关重要的区域的树突棘的稳定性来调节的，包括海马体。小gtpase是海马神经元树突棘形成、稳定性和形态的有效调节因子。通过在小鼠中使用小GTPase蛋白谱分析，我们发现海马CA3区突触Rap1水平升高是对不断升级的间歇性应激的反应。然后，我们证明CA3中Rap1的增加本身足以产生与压力相关的树突脊柱和认知表型。此外，利用超分辨率成像，我们研究了Rap1转运到突触的模式可能是其对选择的树突棘亚型稳定性影响的基础。这些发现阐明了在海马体中异常的Rap1调节参与了应激的心理生物学效应。间断性约束应激降低CA3区的任务依赖性参与间断性约束应激降低CA3区的树突脊柱稳定性间断性约束应激增加CA3区的Rap1突触水平，增加CA3区的Rap1降低树突脊柱密度，损害认知；细胞神经科学;分子神经科学;神经科学
The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress. We then demonstrate that increased Rap1 in the CA3 is sufficient in and of itself to produce stress-relevant dendritic spine and cognitive phenotypes. Further, using super-resolution imaging, we investigate how the pattern of Rap1 trafficking to synapses likely underlies its effects on the stability of select dendritic spine subtypes. These findings illuminate the involvement of aberrant Rap1 regulation in the hippocampus in contributing to the psychobiological effects of stress. Intermittent restraint stress reduces the task-dependent engagement of the CA3 region Intermittent restraint stress reduces dendritic spine stability in the CA3 region Intermittent restraint stress increases the synaptic levels of Rap1 in the CA3 region Increased CA3-region Rap1 reduces dendritic spine density and impairs cognition Biological sciences; Cellular neuroscience; Molecular neuroscience; Neuroscience
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DOI：
10.1073/pnas.1003825107
发表时间：
2010-07-20
影响因子：
11.1
作者：
Chen, Yuncai;Rex, Christopher S.;Baram, Tallie Z.
通讯作者：
Baram, Tallie Z.
影响因子：
--
作者：
Dwivedi, Yogesh;Mondal, Amal C.;Pandey, Ghanshyam N.
通讯作者：
Pandey, Ghanshyam N.
影响因子：
1.7
作者：
Funk AJ;Rumbaugh G;Harotunian V;McCullumsmith RE;Meador-Woodruff JH
通讯作者：
Meador-Woodruff JH
影响因子：
6.8
作者：
Chenani, Alireza;Weston, Ghabiba;Ulivi, Alessandro F.;Castello-Waldow, Tim P.;Huettl, Rosa-Eva;Chen, Alon;Attardo, Alessio
通讯作者：
Attardo, Alessio
影响因子：
4.7
作者：
Cahill ME;Browne CJ;Wang J;Hamilton PJ;Dong Y;Nestler EJ
通讯作者：
Nestler EJ