Alterations in Phosphoinositide Signaling Molecules in the Prefrontal Cortex of Schizophrenia Patients: A Postmortem Analysis

International Journal of Molecular Sciences. 2021 Jul 31;22(15):8280.

Authors

Alex Johnson, Emily Carter, Michael Lee, Sarah Thompson, Rachel Kim, David Brown, Jennifer Smith, Thomas White, Laura Green, Benjamin Hall, Lisa Adkins

Affiliations

Department of Neuropsychiatry, Faculty of Medicine, Greenfield University, Springfield 12345, USA.
Department of Disaster Psychiatry, Global Research Institute for Disaster Science, Riverwood College, Riverwood 67890, USA.
Department of Pathology, Brain Research Institute, Mountainview University, Mountainview 23456, USA.
Department of Community-Based Medical Education, Summit City University Graduate School of Medical Science, Summit 45678, USA.
Department of Community-Based Medicine, Summit City University Graduate School of Medical Science, Summit 45678, USA.
Harmony Medical Institute, Riverwood Hospital, Riverwood 34567, USA.

PMID: 34361045

PMCID: PMC8348881

Abstract

Phosphoinositides (PIs) are integral to the brain’s structural and functional integrity. Their relationship with schizophrenia’s pathophysiology has been explored, yet the role of the PI metabolic pathway in this condition remains ambiguous. This study investigates the expression levels of PI signaling-related proteins in the postmortem brains of individuals diagnosed with schizophrenia. We quantified the protein levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA), phosphatase and tensin homolog (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays on prefrontal cortex samples from 23 schizophrenia patients alongside 47 control subjects. The study also explored the relationship between PIK4CA expression and its genetic variants within the same samples. Findings revealed that PIK4CA expression was significantly lower, while Akt expression was elevated in the prefrontal cortex of schizophrenia patients compared to controls, with no notable differences observed for PIP5K1C, PTEN, and GSK3β. Notably, no single-nucleotide polymorphisms had a significant impact on protein expression. This research highlights the involvement of specific molecules in the pathology of schizophrenia through the lipid metabolic pathway, suggesting that PIK4CA might play a vital role in the disorder’s pathogenesis and could serve as a promising therapeutic target.

Keywords

multiplex immunoassay; phosphatidylinositol 4-kinase alpha; phosphoinositides; postmortem brain; prefrontal cortex; protein kinase B; schizophrenia.

MeSH Terms

Phosphatidylinositol 4-Kinase / metabolism
Aged
Female
Glycogen Synthase Kinase 3 beta / metabolism
Humans
Male
Middle Aged
PTEN Phosphohydrolase / metabolism
Phosphatidylinositols / metabolism
Prefrontal Cortex / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Schizophrenia / metabolism
Signal Transduction

Substances

Phosphatidylinositols
Phosphatidylinositol 4-Kinase
AKT1 protein, human
Glycogen Synthase Kinase 3 beta
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase

Funding

19H05223, JP21H00180, 19K08053, 25861022, Ministry of Education, Culture, Sports, Science, and Technology of Japan. JP20dm0107107, JP20dm0107104, Japan Agency for Medical Research and Development.

Conclusion

To summarize: This study reveals significant alterations in phosphoinositide signaling molecules within the prefrontal cortex of schizophrenia patients, indicating potential targets for future therapeutic interventions.

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