Dataset Information

Transcriptome Analysis of the Mesenteric Adipose and Liver Reveals Novel Mechanisms by Which Prenatal Alcohol Exposure Contributes to Worse Stroke Outcome

ABSTRACT: Prenatal alcohol exposure (PAE) is linked to elevated risk for systemic adult-onset diseases like hypertension, impaired glucose and immune regulation, and in animal models, to impaired recovery from acute onset diseases like cerebrovascular ischemic stroke. Recent evidence suggests that the gastrointestinal system rapidly becomes dysbiotic following cerebrovascular stroke, resulting in systemic inflammation. We hypothesized that a history of PAE would modify the systemic effects of stroke, and transduce exposure-dependent transcriptomic changes in downstream sentinel tissues of the enteric portal circulation that have previously been linked to biobehavioral outcomes in rodent PAE models. Pregnant Sprague Dawley rats were exposed to repeated episodes of vaporized ethanol or room air from gestational day 8 to 19. At 5 months, progeny from each treatment condition were subjected to unilateral endothelin-1 induced occlusion of the middle cerebral artery and outcomes evaluated after 2 days while other progeny stayed stroke-naïve. Stroke induced disabilities were assessed by behavioral assays (adhesive removal, Vibrissae evoked fore-limb placement, circling) and infarct size. The mesenteric adipose tissue and liver transcriptomes were assessed by sequencing, from age-matched stroke-exposed and stroke-naïve offspring. In stroke-naïve animals, pathway analysis identified rRNA processing as downregulated and citric acid cycle as upregulated in mesenteric adipose. Weighted gene correlation network analysis (WGCNA) identified, in the liver of stoke-naïve animals, a moderate but significant correlation between PAE status and necroptosis, a proinflammatory form of programmed cell death (Pearson’s r=0.554, p<0.05). Two days after a stroke, PAE rats exhibited worse neurological scores compared to controls (p<0.05). WGCNA after stroke identified an adipose gene network associated with B cell differentiation and NF-kappa B signaling as moderately correlated with post-stroke neurological function (Pearson's r=0.52, p=0.05). Post-stroke WGCNA also identified a liver proinflammatory gene network strongly correlated with post-stroke neurological function (Pearson's r=-0.63, p<0.01). PAE persistently alters the transcriptome of afferent tissue targets of enteric circulation in adult rat offspring. Moreover, PAE-linked enteric inflammation is correlated to worse outcomes following cerebrovascular ischemic stroke in adulthood. Enteric disturbances may mediate adverse brain health outcomes due to PAE in adulthood.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE217173 | GEO | 2023/08/29

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (<a href="http://ccr.coriell.org/Sections/Collections/NINDS/?SsId=10">the NINDS Repository)</a>, banks phenotypic data and biological samples, including from individuals with cerebrovascular disease, in order to facilitate gene discovery in neurological disorders. Those samples are used in a number of studies, and genotyping data from studies using this resource are encouraged to be shared via dbGaP. Many studies have already shared data in this fashion, which in turn, can be linked back to the biologicals banked at the NINDS Repository. Stroke is the third leading cause of death in the United States, and is an acute neurological event leading to death of neural tissues. Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are hemorrhagic, resulting from bleeding into the brain. Samples available in <a href="http://ccr.coriell.org/Sections/Collections/NINDS/Cerebrovascular.aspx?PgId=190&coll=ND">cerebrovascular disease</a> in the NINDS Repository, include but are not limited to those from individuals affected with the following: ischemic stroke, hemorrhagic stroke, intracranial aneurysm (both ruptured and unruptured), transient ischemic attack, arteriovenous malformations, and others. Many studies contribute to the NINDS Repository collection in an ongoing manner and others are being added regularly. These studies include samples from the Vitamin Intervention for Stroke Prevention (VISP) study, the Ischemic Stroke Genetics Study (ISGS), the Familial Intracranial Aneurysm study, and many others. There is also an associated Control collection (see <a href="./study.cgi?id=phs000004">dbGaP</a> and <a href="http://ccr.coriell.org/Sections/Collections/NINDS/Population.aspx?PgId=194&coll=ND"> Coriell</a>). Others studies may use cases from the NINDS repository, controls from the NINDS repository, as well as cases, and controls, from other sources. A subset of subjects from The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (the NINDS Repository): Cerebrovascular Disease/Stroke Study was utilized in the <a href="./study.cgi?id=phs000102">Ischemic Stroke Genetics Study (ISGS)</a> study.

Dataset Information

Transcriptome Analysis of the Mesenteric Adipose and Liver Reveals Novel Mechanisms by Which Prenatal Alcohol Exposure Contributes to Worse Stroke Outcome

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets