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Single nuclei RNAseq of rat area postrema and nucleus tractus solitarius

ABSTRACT: Single nuclei RNAseq of rat area postrema and nucleus tractus solitarius

PROVIDER: PRJNA705705 | ENA |

REPOSITORIES: ENA

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Single nuclei RNAseq of rat area postrema and nucleus tractus solitarius

Project description:We performed single-nuclei RNAseq of Sprague Dawley rat area postrema and nucleus tractus solitarius brain samples to identify cellular subtypes.

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Single nuclei RNAseq of rat area postrema and nucleus tractus solitarius after GDF15 treatment

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Single nuclei RNAseq of male rat area postrema and nucleus tractus solitarius after cisplatin treatment

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Single nuclei RNAseq of rat area postrema and nucleus tractus solitarius after GDF15 treatment

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Single-nuclei RNA-seq of the nucleus tractus solitarii and area postrema at for baseline and LPS-activated cell types

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Area postrema cell types that mediate nausea-associated behaviors

Project description:Nausea, the unpleasant sensation of visceral malaise, remains a mysterious process. The area postrema is implicated in some nausea responses, and contains poorly understood brain-resident sensory neurons that are anatomically privileged to detect bloodborne signals. To investigate nausea mechanisms, we built an area postrema cell atlas through single-nucleus RNA sequencing, revealing a few neuron types. Using mouse genetic tools for cell-specific manipulation, we discovered excitatory neurons that induce nausea-related behaviors, with one neuron type mediating aversion imposed by multiple poisons. Nausea-associated responses were observed to agonists of identified area postrema receptors, and suppressed by targeted cell ablation and/or gene knockout. Anatomical mapping revealed a distributed network of long-range excitatory but not inhibitory projections with subtype-specific patterning. These studies reveal the basic organization of area postrema nausea circuitry, and provide a framework towards understanding and therapeutically controlling nausea.

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Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation.

Project description:Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control.

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Area postrema cell types that mediate nausea-associated behaviors

Project description:Area postrema cell types that mediate nausea-associated behaviors

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The transcriptome of the medullary area postrema: The thirsty rat, the hungry rat and the hypertensive rat

Project description:The area postrema (AP) is a sensory circumventricular organ characterised by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague Dawley (SD) and Wistar Kyoto (WKY) rat and present here a comprehensive catalogue of gene expression, focussing specifically on the population of ion channels, receptors and G protein-coupled receptors (GPCRs) expressed in this sensory tissue; of the GPCRs expressed in the rat AP we identified ~36% that are orphans having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72-hours dehydration (DSD) and 48-hours fasting (FSD) and have performed microarrays under these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat (SHR) AP compared to the normotensive WKY controls however. Finally, analysis of these ‘hypertension-related’ elements revealed genes that are involved in both the regulation of blood pressure and immune function and as such are excellent targets for further study. Using Affymetrix microarrays (Rat 230:2.0) we anaysed the transcriptome of the area postrema. Each microarray in the study represents an independent biological replicate of 5 animals.

2011-01-22 | E-GEOD-26660 | biostudies-arrayexpress

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