title: Decreased VEGFR2 expression and increased phosphorylated Akt1 in the prefrontal cortex of individuals with schizophrenia.
abstract: The Akt signaling pathway involves various cellular processes and depends on extracellular stimuli. Since Akt signaling participates in cytoprotection, synapse plasticity, axon extension, and neurotransmission in the nervous system, alteration in Akt signaling might be a potential cause of schizophrenia. In this study, we performed multiplex fluorescent bead based immunoassays for members of the Akt signaling pathway in postmortem brains of controls and patients with schizophrenia. Vascular endothelial growth factor receptor 2 (VEGFR2/KDR) was significantly decreased in the prefrontal cortex (PFC) of patients with schizophrenia, and the expression level of VEGFR2 was inversely correlated with the positive symptom subscale of the Diagnostic Instrument for Brain Studies (DIBS) in patients with schizophrenia. There was also an increase in phosphorylated Akt1 in the PFC in the patients, though the ratio of phospho/total Akt1 is not significantly different. In the nucleus accumbens (NAcc) there was no significant difference in expression and phosphorylation levels of Akt signaling proteins. Genetic analysis revealed a significant correlation of a SNP of KDR (rs7692791) with ERK1/2 and Akt1 phospho/total rates. Since VEGFR2 participates in angiogenesis and neurotrophic activation, either or both functions might be responsible for onset of schizophrenia.
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan. Electronic address: mhino@fmu.ac.jp.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Hino
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Kunii
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Matsumoto
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Wada
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nagaoka
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan; Department of Psychiatry, Aizu Medical Center, School of Medicine, Fukushima Medical University, 969-3492 Fukushima, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Niwa
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, 951-8585 Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathological Neuroscience, Brain Research Institute, Niigata University, 951-8585 Niigata, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Department of Community-based Medical Education/Department of Community-based Medicine, Nagoya City University Graduate School of Medical Science, Japan; Choju Medical Institute, Fukushimura Hospital, 441-8124, Aichi, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, 441-8124, Aichi, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashizume
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, 441-8124, Aichi, Japan.
authors.forename: Sakon
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan.
authors.forename: Hirooki
authors.initials: H
authors.lastname: Yabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt signaling; Multiplex fluorescent bead based immunoassay; Postmortem brain; SNPs; Schizophrenia; VEGFR2