Kalirin-7, an important component of excitatory synapses, is regulated by estradiol in hippocampal neurons.
Kalirin-7, an important component of excitatory synapses, is regulated by estradiol in hippocampal neurons.
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DOI：
10.1002/hipo.20780
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发表时间：
2011-06
期刊：
影响因子：
3.5
通讯作者：
Eipper, Betty A.
中科院分区：
文献类型：
--
作者：
Ma, Xin-Ming;Huang, Jian-Ping;Kim, Eun-Ji;Zhu, Qing;Kuchel, George A.;Mains, Richard E.;Eipper, Betty A.
在体外和体内实验中，Escherichia coli可促进海马神经元树突棘和兴奋性突触的形成，但其机制尚不完全清楚。Kalirin-7（Kal 7）是Kalirin在成年海马中的主要同种型，是定位于突触后密度的Rho GDP/GTP交换因子。在海马中，Kal 7和雌二醇受体（ER）α在中间神经元的子集中高度表达。Kal 7的过度表达引起海马神经元棘密度和大小的增加。为了确定Kalirin是否可能在雌二醇对脊柱形成的影响中发挥作用，在卵巢切除大鼠的海马中检查Kal 7表达。雌二醇替代增加了卵巢切除大鼠CA 1锥体神经元和中间神经元的Kal 7染色。Ekaline处理培养的海马神经元增加Kal 7水平在突触后侧的兴奋性突触和增加兴奋性突触的数量沿着锥体神经元的树突。这些增加是通过ERα介导的，因为选择性ERα激动剂，而不是选择性ERβ激动剂，在培养的海马神经元中引起Kal 7水平和兴奋性突触数量的类似增加。当使用Kal 7特异性shRNA降低Kal 7表达时，兴奋性突触的密度降低，雌二醇不再能够增加突触形成。外源性Kal 7在海马中间神经元中的表达导致GAD 65染色水平降低。用荷包牡丹碱抑制GABA能传递产生Kal 7表达的稳健增加。这些研究表明Kal 7在雌二醇介导的突触可塑性机制中起关键作用。
Estradiol enhances the formation of dendritic spines and excitatory synapses in hippocampal neurons in vitro and in vivo, but the underlying mechanisms are not fully understood. Kalirin-7 (Kal7), the major isoform of Kalirin in the adult hippocampus, is a Rho GDP/GTP exchange factor localized to post-synaptic densities. In the hippocampus, both Kal7 and estradiol receptor (ER) α are highly expressed in a subset of interneurons. Over-expression of Kal7 caused an increase in spine density and size in hippocampal neurons. To determine whether Kalirin might play a role in the effects of estradiol on spine formation, Kal7 expression was examined in the hippocampus of ovariectomized rats. Estradiol replacement increased Kal7 staining in both CA1 pyramidal neurons and interneurons in ovariectomized rats. Estradiol treatment of cultured hippocampal neurons increased Kal7 levels at the post-synaptic side of excitatory synapses and increased the number of excitatory synapses along the dendrites of pyramidal neurons. These increases were mediated via ERα because a selective ERα agonist, but not a selective ERβ agonist, caused a similar increase in both Kal7 levels and excitatory synapse number in cultured hippocampal neurons. When Kal7 expression was reduced using a Kal7-specific shRNA, the density of excitatory synapses was reduced and estradiol was no longer able to increase synapse formation. Expression of exogenous Kal7 in hippocampal interneurons resulted in decreased levels of GAD65 staining. Inhibition of GABAergic transmission with bicuculline produced a robust increase in Kal7 expression. These studies suggest Kal7 plays a key role in the mechanisms of estradiol-mediated synaptic plasticity.
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影响因子：
16.2
作者：
Elias, Guillermo M.;Funke, Lars;Nicoll, Roger A.
通讯作者：
Nicoll, Roger A.
影响因子：
5.3
作者：
Ledoux, VA;Woolley, CS
通讯作者：
Woolley, CS
影响因子：
2.5
作者：
González-Burgos, I;Alejandre-Gómez, M;Cervantes, M
通讯作者：
Cervantes, M
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T
DOI：
10.1073/pnas.97.16.9287
发表时间：
2000-08-01
影响因子：
11.1
作者：
Feng, J;Yan, Z;Greengard, P
通讯作者：
Greengard, P