RGD Reference Report - A combined metabonomic and proteomic approach identifies frontal cortex changes in a chronic phencyclidine rat model in relation to human schizophrenia brain pathology. - Rat Genome Database

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A combined metabonomic and proteomic approach identifies frontal cortex changes in a chronic phencyclidine rat model in relation to human schizophrenia brain pathology.

Authors: Wesseling, Hendrik  Chan, Man K  Tsang, T M  Ernst, Agnes  Peters, Fabian  Guest, Paul C  Holmes, Elaine  Bahn, Sabine 
Citation: Wesseling H, etal., Neuropsychopharmacology. 2013 Nov;38(12):2532-44. doi: 10.1038/npp.2013.160. Epub 2013 Jul 3.
RGD ID: 11571618
Pubmed: PMID:23942359   (View Abstract at PubMed)
PMCID: PMC3799075   (View Article at PubMed Central)
DOI: DOI:10.1038/npp.2013.160   (Journal Full-text)

Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms. The findings were compared with results from a proteomic profiling of post-mortem prefrontal cortex from SCZ patients and with relevant findings in the literature. Through this approach, we identified proteomic alterations in glutamate-mediated Ca(2+) signaling (Ca(2+)/calmodulin-dependent protein kinase II, PPP3CA, and VISL1), mitochondrial function (GOT2 and PKLR), and cytoskeletal remodeling (ARP3). Metabonomic profiling revealed changes in the levels of glutamate, glutamine, glycine, pyruvate, and the Ca(2+) regulator taurine. Effects on similar pathways were also identified in the prefrontal cortex tissue from human SCZ subjects. The discovery of similar but not identical proteomic and metabonomic alterations in the chronic PCP rat model and human brain indicates that this model recapitulates only some of the molecular alterations of the disease. This knowledge may be helpful in understanding mechanisms underlying psychosis, which, in turn, can facilitate improved therapy and drug discovery for SCZ and other psychiatric diseases. Most importantly, these molecular findings suggest that the combined use of multiple models may be required for more effective translation to studies of human SCZ.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
schizophrenia  ISOActr3 (Rattus norvegicus)11571618; 11571618protein:decreased expression:frontal cortex (rat)RGD 
schizophrenia  IEP 11571618; 11571618protein:decreased expression:frontal cortex (rat)RGD 
schizophrenia  ISOGot2 (Rattus norvegicus)11571618; 11571618protein:decreased expression:frontal cortex (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Actr3  (actin related protein 3)
Got2  (glutamic-oxaloacetic transaminase 2)

Genes (Mus musculus)
Actr3  (ARP3 actin-related protein 3)
Got2  (glutamatic-oxaloacetic transaminase 2, mitochondrial)

Genes (Homo sapiens)
ACTR3  (actin related protein 3)
GOT2  (glutamic-oxaloacetic transaminase 2)


Additional Information