Abstract
Schizophrenia is a debilitating mental disorder that affects approximately 1% of the world population, yet the disorder is not very well understood. The genetics of schizophrenia is very heterogenous, making it hard to pinpoint specific alterations that may cause the disorder. However, there is growing evidence from human studies suggesting a link between alterations in the 14-3-3 family and schizophrenia. The 14-3-3 proteins are abundantly expressed in the brain and are involved in many important cellular processes. Knockout of 14-3-3 proteins in mice has been shown to cause molecular, structural, and behavioral alterations associated with schizophrenia. Thus, 14-3-3 animal models allow for further exploration of the relationship between 14-3-3 and schizophrenia as well as the study of schizophrenia pathology. This review considers evidence from both human and animal model studies that implicate the 14-3-3 family in schizophrenia. In addition, possible mechanisms by which alterations in 14-3-3 proteins may contribute to schizophrenia-like phenotypes such as dopaminergic, glutamatergic, and cytoskeletal dysregulations are discussed.
Highlights
Schizophrenia is a psychiatric disorder that affects both cognition and behavior
We found that the lateral septum (LS), which shows increased c-Fos activity after open field test (OFT) in dorsal HPC (dHPC) injected mice, has mono-synaptic connections with the dHPC (Zhang et al, 2022)
One interesting and promising route of study in schizophrenia is the role of 14-3-3 proteins
Summary
Schizophrenia is a psychiatric disorder that affects both cognition and behavior. The symptoms of schizophrenia are generally grouped into positive, negative, and cognitive symptoms including hallucinations, delusions, anhedonia, and reductions in attention and memory. Antipsychotic drugs are typically prescribed to treat the symptoms of schizophrenia and have been a useful therapeutic These drugs can help alleviate the positive symptoms, and to a lesser extent the negative symptoms of the disorder, but are ineffective in treating cognitive symptoms (Freedman, 2003). In the nervous system, published studies have indicated the involvement of 14-3-3 proteins in intracellular signaling, cell division and differentiation, apoptosis, and ion channel function (Berg et al, 2003). Both human and animal studies have implicated 14-3-3 in several neurodegenerative and psychiatric diseases, including schizophrenia (Foote and Zhou, 2012). This review will discuss the results of some of the genetic and animal model studies that provide evidence for the link between 14-3-3 and schizophrenia
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