Dataset Information

Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia.

ABSTRACT: Increasing evidence suggests that olfactory dysfunction is an endophenotype of schizophrenia, and thus the olfactory system can be studied both in relation to this sensory dysfunction and also as a means of examining pathophysiologic mechanisms of schizophrenia. In this study, we examined human olfactory neuroepithelial (ON) biopsy tissues and their in vitro culture cells for ligand-induced guanine nucleotide-binding protein (G protein) activation and downstream signaling. We assessed the binding of a nonhydrolyzable GTP analogue [(35)S]GTP?S binding to specific G protein subtypes in response to odorants, dopamine, or serotonin in ON cell membranes from matched schizophrenia-control subjects. In response to odorant mixtures, we found decreased [(35)S]GTP?S binding to G?s/olf in schizophrenia patients. These changes were not mediated by mRNA expression of key molecules of G protein coupling, including adenylate cyclase III (ACIII), protein kinase A (PKA), protein kinase C? (PKC?), or G?s or G?olf in ON cells or ON biopsy tissues. In contrast, dopamine (DA)- and serotonin (5HT)-induced S(35)-GTP?S binding to G?s/olf and G?q/11 were significantly increased in schizophrenia cases, while these parameters were strikingly reduced by in vitro treatment with antipsychotics. Patients with schizophrenia exhibit increases in electrolfactogram (EOG) recordings, suggesting enhanced odorant-induced activation. Our results of decreased odorant-induced G protein activation may point further downstream for underlying mechanisms for increased EOG measures. Increased G protein activation in response to DA and 5HT may suggest increased postreceptor DA or 5HT signaling as an additional mechanism of dopaminergic or serotonergic dysregulation in schizophrenia.

SUBMITTER: Borgmann-Winter KE

PROVIDER: S-EPMC4753598 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia.

Borgmann-Winter Karin E KE Wang Hoau-Yan HY Ray Rabindranath R Willis Brooke R BR Moberg Paul J PJ Rawson Nancy E NE Gur Raquel E RE Turetsky Bruce I BI Hahn Chang-Gyu CG

Schizophrenia bulletin 20150915 2

Increasing evidence suggests that olfactory dysfunction is an endophenotype of schizophrenia, and thus the olfactory system can be studied both in relation to this sensory dysfunction and also as a means of examining pathophysiologic mechanisms of schizophrenia. In this study, we examined human olfactory neuroepithelial (ON) biopsy tissues and their in vitro culture cells for ligand-induced guanine nucleotide-binding protein (G protein) activation and downstream signaling. We assessed the bindin ...[more]

PMID: 26373539

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Project description:IntroductionThere is mounting evidence that visual perception abnormalities in schizophrenia are partly explained by a dysfunction of the lateral occipital complex (LO). We previously demonstrated that schizophrenia patients had broader topography and reduced magnitude of activity of LO. However, the functional connectivity of LO with other brain regions during visual perception has not been directly investigated in schizophrenia.Materials and methodsEighteen patients with schizophrenia and eighteen matched controls performed a backward masking task during functional magnetic resonance imaging (fMRI). Stimulus onset asynchronies were manipulated to change the level of target visibility. To examine connectivity with LO function we conducted psychophysiological interactions (PPI) analyses using: 1) a region of interest (ROI) approach and 2) a whole brain analysis. ROIs were defined based on a contrast of trials on which a target was presented versus null trials in which no stimuli were presented.ResultsEleven ROIs were identified. Both groups showed similar strength of coupling between LO and the 11 ROIs when visibility was not taken into account. Healthy controls showed clear changes in coupling between LO and prefrontal and parietal regions as a function of target visibility (higher coupling with more visible targets). In comparison, patients showed reduced dynamic coupling with LO in the right superior frontal gyrus (significant after correcting for multiple comparisons) and a trend for reduced coupling in the left precuneus and left inferior frontal regions. Whole brain analysis identified additional regions that showed dynamic coupling with LO in healthy controls, but not in patients.DiscussionThe increased coupling between LO and higher-level parietal and prefrontal regions during visual awareness in healthy controls likely reflects visual reentrant processing. The lack of modulation of coupling between LO and key prefrontal and parietal regions found in schizophrenia may partly reflect abnormalities in LO tuning. The altered LO coupling may contribute to visual perception abnormalities in schizophrenia.

Dataset Information

Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia.

Publications

Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia.

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