Kalirin‐7, an important component of excitatory synapses, is regulated by estradiol in hippocampal neurons
- 25 May 2011
- journal article
- research article
- Published by Wiley in Hippocampus
- Vol. 21 (6), 661-677
- https://doi.org/10.1002/hipo.20780
Abstract
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 postsynaptic densities. In the hippocampus, both Kal7 and estrogen receptor α (ERα) 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 postsynaptic 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.Keywords
This publication has 98 references indexed in Scilit:
- Estrous cycle regulates activation of hippocampal Akt, LIM kinase, and neurotrophin receptors in C57BL/6 miceNeuroscience, 2008
- Regulation of Kalirin by Cdk5Journal of Cell Science, 2008
- Balancing Structure and Function at Hippocampal Dendritic SpinesAnnual Review of Neuroscience, 2008
- Coordination of Synaptic Adhesion with Dendritic Spine Remodeling by AF-6 and Kalirin-7Journal of Neuroscience, 2008
- Uncovering the mechanisms of estrogen effects on hippocampal functionFrontiers in Neuroendocrinology, 2008
- Spine Expansion and Stabilization Associated with Long-Term PotentiationJournal of Neuroscience, 2008
- Estrogen and aging affect synaptic distribution of phosphorylated LIM kinase (pLIMK) in CA1 region of female rat hippocampusNeuroscience, 2008
- Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic SpinesNeuron, 2007
- Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNSFrontiers in Neuroendocrinology, 2006
- Synapse-specific regulation of AMPA receptor function by PSD-95Proceedings of the National Academy of Sciences of the United States of America, 2006