TY - JOUR
T1 - Proteomic analysis of the maternal protein restriction rat model for schizophrenia
T2 - Identification of translational changes in hormonal signaling pathways and glutamate neurotransmission
AU - Guest, Paul C.
AU - Urday, Sebastian
AU - Ma, Dan
AU - Stelzhammer, Viktoria
AU - Harris, Laura W.
AU - Amess, Bob
AU - Pietsch, Sandra
AU - Oheim, Christin
AU - Ozanne, Susan E.
AU - Bahn, Sabine
N1 -
Funding: Stanley Medical Research Institute British Heart Foundation
Innovative Medicines Initiative Dutch Fund. Grant Number: 0908.
PY - 2012/12/17
Y1 - 2012/12/17
N2 - 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.
AB - 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.
KW - Animal proteomics
KW - In silico analysis
KW - Low protein rat
KW - MS
KW - Multiplex immunoassay
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84871278221&partnerID=8YFLogxK
UR - https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/pmic.201200376
U2 - 10.1002/pmic.201200376
DO - 10.1002/pmic.201200376
M3 - Article
C2 - 23071080
AN - SCOPUS:84871278221
SN - 1615-9853
VL - 12
SP - 3580
EP - 3589
JO - Proteomics
JF - Proteomics
IS - 23-24
ER -