title: Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We characterized behavioral and functional changes in transgenic mice that express an isoform-independent 14-3-3 inhibitor peptide in the brain.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Collectively, our data provide a link between 14-3-3 dysfunction, synaptic alterations, and schizophrenia-associated behavioral deficits.
authors: Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, Florida.
authors: Molly
authors: M
authors: Foote
authors: Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, Florida.
authors: Haifa
authors: H
authors: Qiao
authors: Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, Florida.
authors: Kourtney
authors: K
authors: Graham
authors: Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, Florida.
authors: Yuying
authors: Y
authors: Wu
authors: Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, Florida.. Electronic address: yzhou@fsu.edu.
authors: Yi
authors: Y
authors: Zhou
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D051177:Catenins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003024:Clozapine / Q000008:administration & dosage; D051338:Cofilin 1 / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D065808:Prepulse Inhibition / Q000187:drug effects; D011506:Proteins / Q000235:genetics; D011954:Receptors, Dopamine / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D009435:Synaptic Transmission; D000095002:Delta Catenin
chemical_list: D048948:14-3-3 Proteins; D014150:Antipsychotic Agents; D051177:Catenins; D051338:Cofilin 1; D011506:Proteins; D011954:Receptors, Dopamine; C443131:difopein; D003024:Clozapine; D006220:Haloperidol; D004298:Dopamine; D000095002:Delta Catenin
keywords: 14-3-3 Proteins; Dendritic spines; Neurotransmission; Prefrontal cortex; Schizophrenia; Transgenic mouse model