Dataset Information

Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

ABSTRACT: Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain. Across 2 different sites and protocols, Nrg1 mutants demonstrated deficits in prepulse inhibition, a measure of sensorimotor gating, that is, disrupted in schizophrenia; these deficits were partially reversed by acute treatment with second, but not first-, generation antipsychotic drugs. However, Nrg1 mutants did not show a specific deficit in latent inhibition, a measure of selective attention that is also disrupted in schizophrenia. In contrast, in a "what-where-when" object recognition memory task, Nrg1 mutants displayed sex-specific (males only) disruption of "what-when" performance, indicative of impaired temporal aspects of episodic memory. Differential metabolomic profiling revealed that these behavioral phenotypes were accompanied, most prominently, by alterations in lipid metabolism pathways. This study is the first to associate these novel physiological mechanisms, previously independently identified as being abnormal in schizophrenia, with disruption of NRG1 function. These data suggest novel mechanisms by which compromised neuregulin function from birth might lead to schizophrenia-relevant behavioral changes in adulthood.

SUBMITTER: O'Tuathaigh CMP

PROVIDER: S-EPMC5581893 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

O'Tuathaigh Colm M P CMP Mathur Naina N O'Callaghan Matthew J MJ MacIntyre Lynsey L Harvey Richard R Lai Donna D Waddington John L JL Pickard Benjamin S BS Watson David G DG Moran Paula M PM

Schizophrenia bulletin 20170901 5

Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a ma ...[more]

PMID: 28338897

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Project description:Post-harvest wet coffee processing is a commonly applied method to transform coffee cherries into green coffee beans through depulping or demucilaging, fermentation, washing, soaking, drying, and dehulling. Multiple processing parameters can be modified and thus influence the coffee quality (green coffee beans and cup quality). The present study aimed to explore the impacts of these parameters, including processing type (depulping or demucilaging), fermentation duration, and application of soaking, on the microbial community dynamics, metabolite compositions of processing waters (fermentation and soaking) and coffee beans, and resulting cup quality through a multiphasic approach. A large-scale wet coffee processing experiment was conducted with Coffea arabica var. Catimor in Yunnan (China) in duplicate. The fermentation steps presented a dynamic interaction between constant nutrient release (mainly from the cherry mucilage) into the surrounding water and active microbial activities led by lactic acid bacteria, especially Leuconostoc and Lactococcus. The microbial communities were affected by both the processing type and fermentation duration. At the same time, the endogenous coffee bean metabolism remained active at different stages along the processing, as could be seen through changes in the concentrations of carbohydrates, organic acids, and free amino acids. Among all the processing variants tested, the fermentation duration had the greatest impact on the green coffee bean compositions and the cup quality. A long fermentation duration resulted in a fruitier and more acidic cup. As an ecological alternative for the depulped processing, the demucilaged processing produced a beverage quality comparable to the depulped one. The application of soaking, however, tempered the positive fermentation effects and standardized the green coffee bean quality, regardless of the preceding processing practices applied. Lastly, the impact strength of each processing parameter would also depend on the coffee variety used and the local geographical conditions. All these findings provide a considerable margin of opportunities for future coffee research.

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Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

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Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

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