RGD Reference Report - Pro-apoptotic Par-4 and dopamine D2 receptor in temporal cortex in schizophrenia, bipolar disorder and major depression. - Rat Genome Database

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Pro-apoptotic Par-4 and dopamine D2 receptor in temporal cortex in schizophrenia, bipolar disorder and major depression.

Authors: Glantz, LA  Gilmore, JH  Overstreet, DH  Salimi, K  Lieberman, JA  Jarskog, LF 
Citation: Glantz LA, etal., Schizophr Res. 2010 May;118(1-3):292-9. doi: 10.1016/j.schres.2009.12.027. Epub 2010 Jan 13.
RGD ID: 9835359
Pubmed: PMID:20067857   (View Abstract at PubMed)
PMCID: PMC2856798   (View Article at PubMed Central)
DOI: DOI:10.1016/j.schres.2009.12.027   (Journal Full-text)

Although the etiology of schizophrenia remains unknown, diverse neuropathological evidence suggests a disorder of synaptic connectivity. Apoptosis is a form of cell death that helps determine synaptic circuitry during neurodevelopment and altered regulation of apoptosis has been implicated in schizophrenia. Prostate apoptosis response-4 (Par-4) is an upstream regulator of apoptosis preferentially localized to synapses. Brain Par-4 levels are upregulated in response to pro-apoptotic stimuli in rodent models and in patients with classic neurodegenerative diseases. Recently, Par-4 was also found to form a complex with the dopamine D2 receptor (D2DR) in competition with the calcium-binding protein calmodulin, implicating Par-4 as an important regulatory component in normal dopamine signaling. Interestingly, mutant mice with disrupted Par-4/D2DR interaction demonstrated depressive-like behaviors, suggesting a potential role for Par-4 in both depression and schizophrenia. In this study, Par-4, D2DR and calmodulin protein levels were measured using semiquantitative Western blotting in postmortem temporal cortex in subjects with schizophrenia, major depression and bipolar disorder. Compared to normal controls, mean Par-4 levels appeared slightly lower in schizophrenia and bipolar disorder. However, in major depression, Par-4 was decreased by 67% compared to normal controls. No differences were found between any groups for calmodulin or for the D2DR 48 kDa band. The D2DR 98 kDa band was lower by 50% in the schizophrenia compared to control groups. Changes in the Par-4/D2DR signaling pathway represent a novel mechanism that may link apoptotic and dopamine signaling pathways in major depression and schizophrenia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
major depressive disorder  IEP 9835359protein:decreased expression:brain:RGD 
major depressive disorder  ISOPAWR (Homo sapiens)9835359; 9835359protein:decreased expression:brain:RGD 
schizophrenia  IEP 9835359protein:decreased homodimerization:temporal cortex:RGD 
schizophrenia  ISODRD2 (Homo sapiens)9835359; 9835359protein:decreased homodimerization:temporal cortex:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd2  (dopamine receptor D2)
Pawr  (pro-apoptotic WT1 regulator)

Genes (Mus musculus)
Drd2  (dopamine receptor D2)
Pawr  (PRKC, apoptosis, WT1, regulator)

Genes (Homo sapiens)
DRD2  (dopamine receptor D2)
PAWR  (pro-apoptotic WT1 regulator)


Additional Information