TY - JOUR
T1 - Evidence for altered phosphoinositide signaling-associated molecules in the postmortem prefrontal cortex of patients with schizophrenia
AU - Kunii, Yasuto
AU - Matsumoto, Junya
AU - Izumi, Ryuta
AU - Nagaoka, Atsuko
AU - Hino, Mizuki
AU - Shishido, Risa
AU - Sainouchi, Makoto
AU - Akatsu, Hiroyasu
AU - Hashizume, Yoshio
AU - Kakita, Akiyoshi
AU - Yabe, Hirooki
N1 - Funding Information:
Funding: This research was funded by the Strategic Research Program for Brain Sciences from AMED, grant numbers JP20dm0107107 (H.Y.) ,JP20dm0107104 (A.K.) and JP21dm020707(Y.K.); the Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, grant numbers 19H05223 (Y.K.) and JP21H00180 (Y.K.); the Grants-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, grant number 19K08053 (Y.K.); the Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science, grant number 25861022 (J.M.); and the Collaborative Research Project of Brain Research Institute, Niigata University, grant number 201917 (Y.K.).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - 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.
AB - 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.
KW - Multiplex immunoassay
KW - Phosphatidylinositol 4-kinase alpha
KW - Phosphoinositides
KW - Postmortem brain
KW - Prefrontal cortex
KW - Protein kinase B
KW - Schizophrenia
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U2 - 10.3390/ijms22158280
DO - 10.3390/ijms22158280
M3 - Article
C2 - 34361045
AN - SCOPUS:85111428821
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 15
M1 - 8280
ER -