Proteomic analysis of the maternal protein restriction rat model for schizophrenia: Identification of translational changes in hormonal signaling pathways and glutamate neurotransmission

Paul C. Guest*, Sebastian Urday, Dan Ma, Viktoria Stelzhammer, Laura W. Harris, Bob Amess, Sandra Pietsch, Christin Oheim, Susan E. Ozanne, Sabine Bahn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have found that some first onset schizophrenia patients show signs of impaired insulin signaling. Also, epidemiological studies have shown that periods of suboptimal nutrition including protein deficiencies during pregnancy can lead to increased incidence of metabolic conditions and psychiatric disorders in the offspring. For these reasons, we have carried out a molecular profiling analysis of blood serum and brain tissues from adult offspring produced by the maternal low protein (LP) rat model. The results showed similar changes to those seen in schizophrenia. Multiplex immunoassay profiling identified changes in the levels of insulin, adiponectin, and leptin along with alterations in inflammatory and vascular system-related proteins such as osteopontin, macrophage colony-stimulating factor 1, and vascular cell adhesion molecule 1. LC-MSE proteomic profiling showed that glutamatergic pathways were altered in frontal cortex, while signaling pathways and cytoskeletal proteins involved in hormonal secretion and synaptic remodeling were altered in the hypothalamus. Taken together, these studies indicate that the LP rat model recapitulates several pathophysiological attributes seen in schizophrenia patients. We propose that the LP model may have utility for drug discovery efforts, especially to identify compounds that modulate the metabolic and glutamatergic systems.

Original languageEnglish
Pages (from-to)3580-3589
Number of pages10
JournalProteomics
Volume12
Issue number23-24
Early online date16 Oct 2012
DOIs
Publication statusPublished - 17 Dec 2012

Bibliographical note



Funding: Stanley Medical Research Institute British Heart Foundation
Innovative Medicines Initiative Dutch Fund. Grant Number: 0908.

Keywords

  • Animal proteomics
  • In silico analysis
  • Low protein rat
  • MS
  • Multiplex immunoassay
  • Schizophrenia

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