system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: 14-3-3 Proteins, Animals, Antipsychotic Agents, Behavior, Animal, Catenins, Cerebral Cortex, Clozapine, Cofilin 1, Dendrites, Disease Models, Animal, Dopamine, Haloperidol, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Prepulse Inhibition, Proteins, Receptors, Dopamine, Schizophrenia, Schizophrenic Psychology, Synaptic Transmission.
user
Does inhibition of 14-3-3 Proteins lead to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice? Context: 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.
assistant
Collectively, our data provide a link between 14-3-3 dysfunction, synaptic alterations, and schizophrenia-associated behavioral deficits. Final Decision: yes