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Decreased VEGFR2 expression and increased phosphorylated Akt1 in the prefrontal cortex of individuals with

Mizuki Hino1, Yasuto Kunii1, Junya Matsumoto1

  • 1Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 960-1295 Fukushima, Japan.

Journal of Psychiatric Research
|August 4, 2016
PubMed

Insights

Schizophrenia may involve altered Akt signaling. Reduced vascular endothelial growth factor receptor 2 (VEGFR2) in the brain correlates with symptom severity, suggesting a role in schizophrenia pathogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • The Akt signaling pathway regulates critical cellular functions, including those in the nervous system.
  • Dysregulation of Akt signaling is implicated in neurological disorders.
  • Its role in schizophrenia, a complex psychiatric condition, warrants further investigation.

Purpose of the Study:

  • To investigate the role of the Akt signaling pathway in the pathophysiology of schizophrenia.
  • To examine the expression and phosphorylation levels of key Akt pathway proteins in postmortem brain samples from schizophrenia patients and controls.

Main Methods:

  • Multiplex fluorescent bead-based immunoassays were used to quantify Akt signaling pathway members.
  • Postmortem brain tissues from the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of schizophrenia patients and controls were analyzed.
  • Genetic analysis of a single nucleotide polymorphism (SNP) in the KDR gene was performed.

Main Results:

  • Vascular endothelial growth factor receptor 2 (VEGFR2/KDR) expression was significantly decreased in the PFC of schizophrenia patients.
  • VEGFR2 levels showed an inverse correlation with positive symptom severity in schizophrenia.
  • Increased phosphorylated Akt1 was observed in the PFC, but the phospho/total ratio was not significantly different.
  • No significant differences in Akt signaling proteins were found in the NAcc.
  • A significant correlation was found between a KDR SNP (rs7692791) and Akt1/ERK1/2 phosphorylation rates.

Conclusions:

  • Reduced VEGFR2 expression in the PFC may contribute to schizophrenia.
  • VEGFR2's roles in angiogenesis and neurotrophic support could be implicated in schizophrenia onset.
  • Further research into the Akt pathway and VEGFR2 is crucial for understanding schizophrenia.
Keywords:
Akt signalingMultiplex fluorescent bead based immunoassayPostmortem brainSNPsSchizophreniaVEGFR2

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