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Seeking novel mammalian genes using transcript profiling and genotyping of a human radiation hybrid panel

ABSTRACT: Seeking novel mammalian genes using transcript profiling and genotyping of a human radiation hybrid panel

PROVIDER: PRJNA120437 | ENA |

REPOSITORIES: ENA

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Seeking novel mammalian genes using transcript profiling and genotyping of a human radiation hybrid panel

Project description:Using a human-hamster radiation hybrid panel (G3), we have mapped loci regulating gene expression due to copy number increase.

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Seeking novel mammalian genes using transcript profiling and genotyping of a human radiation hybrid panel

Project description:Using a human-hamster radiation hybrid panel (G3), we have mapped loci regulating gene expression due to copy number increase. Copy number from radiation hybrid clones were measured relative to the A23 hamster recipient line. Expression from 79 radiation hybrid clones were measured in duplicate and compared to expression of the A23 hamster recipient line (GA_illumina_expression1 and GA_illumina_expression2). Expression of liver, kidney and heart from human and hamster are also included (GA_illumina_expression_R).

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Project description:Cocaine use disorder represents a public health crisis with no FDA-approved medications for its treatment. A growing body of research has detailed the important connections between the brain and the resident population of bacteria in the gut, the gut microbiome in psychiatric disease models. Acute depletion of gut bacteria results in enhanced reward in a mouse cocaine place preference model, and repletion of bacterially-derived short-chain fatty acid (SCFA) metabolites reverses this effect. However, the role of the gut microbiome and its metabolites in modulating cocaine-seeking behavior after prolonged abstinence is unknown. Given that relapse prevention is the most clinically challenging issue in treating substance use disorders, studies examining the effects of microbiome manipulations in relapse-relevant models are critical. Here, Sprague-Dawley rats received either untreated water or antibiotics to deplete the gut microbiome and its metabolites. Rats were trained to self-administer cocaine and subjected to either within-session threshold testing to evaluate motivation for cocaine or 21 days of abstinence followed by a cue-induced cocaine-seeking task to model relapse behavior. Microbiome depletion did not affect cocaine acquisition on an FR1 schedule. However, microbiome-depleted subjects exhibited significantly enhanced motivation for low dose cocaine on a within-session threshold task. Similarly, microbiome depletion increased cue-induced cocaine-seeking following prolonged abstinence. In the absence of a normal microbiome, repletion of bacterially-derived SCFA metabolites reversed the behavioral and transcriptional changes associated with microbiome depletion. These findings suggest that gut bacteria, via their metabolites, are key regulators of drug-seeking behaviors, positioning the microbiome as a potential translational research target.

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Solar exposed skin induces sex-dependent food-seeking behavior

Project description:Considering the distinct physiologies of men and women, it stands to reason that they would react differently to solar exposure, but such a study was never conducted before. Here we show that solar exposure induces food-seeking behavior, food intake and weight gain in males, but not in females, by epidemiological analysis, blood-serum proteomics, UVB-exposed mouse behavioral models and human cohort questionnaires . The underlying mechanism entails increased ghrelin secretion from skin adipocytes into the circulation. UVB irradiation led to p53 transcriptional activation of ghrelin in skin adipocytes, with mouse conditional p53-knockout abolishing UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53–chromatin interaction on the ghrelin promotor, thus blocking ghrelin and, consequently, food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of human physiology in furless animals and may lead to therapeutic opportunities for sex-based treatment of endocrine-related diseases.

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Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking.

Project description:Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking.

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