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Up-regulated 14-3-3β and 14-3-3ζ proteins in prefrontal cortex of subjects with schizophrenia: effect of psychotropic
Guadalupe Rivero1, Ane M Gabilondo1, Jesús A García-Sevilla2
1Department of Pharmacology, University of te Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; BioCruces Health Research Institute and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Abstract:
14-3-3 is a family of conserved regulatory proteins that bind to a multitude of functionally diverse signalling proteins. Various genetic studies and gene expression and proteomic analyses have involved 14-3-3 proteins in schizophrenia (SZ). On the other hand, studies about the status of these proteins in major depressive disorder (MD) are still missing. Immunoreactivity values of cytosolic 14-3-3β and 14-3-3ζ proteins were evaluated by Western blot in prefrontal cortex (PFC) of subjects with schizophrenia (SZ; n=22), subjects with major depressive disorder (MD; n=21) and age-, gender- and postmortem delay-matched control subjects (n=52). The modulation of 14-3-3β and 14-3-3ζ proteins by psychotropic medication was also assessed. The analysis of both proteins in SZ subjects with respect to matched control subjects showed increased 14-3-3β (Δ=33±10%, p<0.05) and 14-3-3ζ (Δ=29±6%, p<0.05) immunoreactivity in antipsychotic-free but not in antipsychotic-treated SZ subjects. Immunoreactivity values of 14-3-3β and 14-3-3ζ were not altered in MD subjects. These results show the specific up-regulation of 14-3-3β and 14-3-3ζ proteins in PFC of SZ subjects and suggest a possible down-regulation of both proteins by antipsychotic treatment.
Insights
14-3-3 proteins are up-regulated in the prefrontal cortex of individuals with schizophrenia, but not major depressive disorder. Antipsychotic treatment may down-regulate these essential regulatory proteins.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- 14-3-3 proteins are crucial regulators of diverse signaling pathways.
- Previous studies implicated 14-3-3 proteins in schizophrenia (SZ), but their role in major depressive disorder (MD) remains unexplored.
- Understanding 14-3-3 protein status in these disorders is vital for potential therapeutic targets.
Purpose of the Study:
- To investigate the levels of 14-3-3β and 14-3-3ζ proteins in the prefrontal cortex (PFC) of patients with SZ and MD.
- To examine the influence of psychotropic medication on 14-3-3 protein expression in SZ patients.
Main Methods:
- Western blot analysis was used to quantify cytosolic 14-3-3β and 14-3-3ζ protein immunoreactivity.
- Samples were obtained from the PFC of individuals diagnosed with SZ (n=22), MD (n=21), and matched controls (n=52).
- Patients were categorized based on antipsychotic treatment status.
Main Results:
- 14-3-3β and 14-3-3ζ protein levels were significantly increased in antipsychotic-free SZ subjects compared to controls (33% and 29%, respectively).
- No significant alterations in 14-3-3β and 14-3-3ζ protein levels were observed in MD subjects compared to controls.
- Antipsychotic treatment appeared to down-regulate the expression of both 14-3-3β and 14-3-3ζ proteins in SZ patients.
Conclusions:
- 14-3-3β and 14-3-3ζ proteins are specifically upregulated in the PFC of individuals with schizophrenia.
- These findings suggest a potential role for 14-3-3 proteins in the pathophysiology of schizophrenia.
- Antipsychotic medications may modulate the levels of 14-3-3 proteins, indicating a possible mechanism of action.
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