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Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities

Kim, I. H. and Rácz, Bence and Wang, H. and Burianek, L. and Weinberg, R. J. and Yasuda, R. and Wetsel, William C. and Soderling, S. H. (2014) Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. JOURNAL OF NEUROSCIENCE, 33 (14). pp. 6081-6092. ISSN 0270-6474

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Abstract

Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knock-out of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestrates de novo actin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines, followed by a progressive loss of spine synapses. This progression of synaptic deficits corresponds with an evolution of distinct cognitive, psychomotor, and social disturbances as the mice age. Together, these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of complex psychiatric disorders.

Item Type: Article
Subjects: Q Science / természettudomány > QP Physiology / élettan
Depositing User: Dr. Bence Rácz
Date Deposited: 23 Sep 2014 13:00
Last Modified: 23 Sep 2014 13:00
URI: http://real.mtak.hu/id/eprint/16160

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