Evidence for altered phosphoinositide signaling-associated molecules in the postmortem prefrontal cortex of patients with schizophrenia

Yasuto Kunii, Junya Matsumoto, Ryuta Izumi, Atsuko Nagaoka, Mizuki Hino, Risa Shishido, Makoto Sainouchi, Hiroyasu Akatsu, Yoshio Hashizume, Akiyoshi Kakita, Hirooki Yabe

Research output: Contribution to journalArticlepeer-review

Abstract

Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3β expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target.

Original languageEnglish
Article number8280
JournalInternational journal of molecular sciences
Volume22
Issue number15
DOIs
Publication statusPublished - 2021 Aug 1

Keywords

  • Multiplex immunoassay
  • Phosphatidylinositol 4-kinase alpha
  • Phosphoinositides
  • Postmortem brain
  • Prefrontal cortex
  • Protein kinase B
  • Schizophrenia

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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