You are here

Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice.

Title: Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice.
10 views
1 downloads
Name(s): Foote, Molly, author
Qiao, Haifa, author
Graham, Kourtney, author
Wu, Yuying, author
Zhou, Yi, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2015-09-15
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The 14-3-3 family of proteins is implicated in the regulation of several key neuronal processes. Previous human and animal studies suggested an association between 14-3-3 dysregulation and schizophrenia. We characterized behavioral and functional changes in transgenic mice that express an isoform-independent 14-3-3 inhibitor peptide in the brain. We recently showed that 14-3-3 functional knockout mice (FKO) exhibit impairments in associative learning and memory. We report here that these 14-3-3 FKO mice display other behavioral deficits that correspond to the core symptoms of schizophrenia. These behavioral deficits may be attributed to alterations in multiple neurotransmission systems in the 14-3-3 FKO mice. In particular, inhibition of 14-3-3 proteins results in a reduction of dendritic complexity and spine density in forebrain excitatory neurons, which may underlie the altered synaptic connectivity in the prefrontal cortical synapse of the 14-3-3 FKO mice. At the molecular level, this dendritic spine defect may stem from dysregulated actin dynamics secondary to a disruption of the 14-3-3-dependent regulation of phosphorylated cofilin. Collectively, our data provide a link between 14-3-3 dysfunction, synaptic alterations, and schizophrenia-associated behavioral deficits.
Identifier: FSU_pmch_25863357 (IID), 10.1016/j.biopsych.2015.02.015 (DOI), PMC4544659 (PMCID), 25863357 (RID), 25863357 (EID), S0006-3223(15)00125-0 (PII)
Keywords: 14-3-3 Proteins, Dendritic spines, Neurotransmission, Prefrontal cortex, Schizophrenia, Transgenic mouse model
Grant Number: R01 NS050355, NS50355
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544659.
Subject(s): 14-3-3 Proteins/antagonists & inhibitors
14-3-3 Proteins/genetics
14-3-3 Proteins/metabolism
Animals
Antipsychotic Agents/administration & dosage
Behavior, Animal/drug effects
Catenins/metabolism
Cerebral Cortex/metabolism
Cerebral Cortex/pathology
Clozapine/administration & dosage
Cofilin 1/metabolism
Dendrites/metabolism
Dendrites/pathology
Disease Models, Animal
Dopamine/metabolism
Haloperidol/administration & dosage
Mice
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Prepulse Inhibition/drug effects
Proteins/genetics
Receptors, Dopamine/metabolism
Schizophrenia/genetics
Schizophrenia/metabolism
Schizophrenia/physiopathology
Schizophrenic Psychology
Synaptic Transmission
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_25863357
Owner Institution: FSU
Is Part Of: Biological psychiatry.
1873-2402
Issue: iss. 6, vol. 78

Choose the citation style.
Foote, M., Qiao, H., Graham, K., Wu, Y., & Zhou, Y. (2015). Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice. Biological Psychiatry. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_25863357