Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series

Alcohol withdrawal syndrome (AWS) is characterized by neuronal hyperexcitability, autonomic dysregulation, and severe negative emotion. The nucleus tractus solitarius (NTS) likely plays a prominent role in the neurological processes underlying these symptoms as it is the main viscerosensory nucleus...

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Autores principales:	Sean J. O’Sullivan, Damani McIntosh-Clarke, James Park, Rajanikanth Vadigepalli, James S. Schwaber
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	alcohol withdrawal neuroinflammation RT-PCR subphenotypes single-cell heterogeneity microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/ee4e039aba274d2a8f26a523ce0f09d5
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spelling	oai:doaj.org-article:ee4e039aba274d2a8f26a523ce0f09d52021-11-19T12:41:03ZSingle Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series1662-513710.3389/fnsys.2021.739790https://doaj.org/article/ee4e039aba274d2a8f26a523ce0f09d52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnsys.2021.739790/fullhttps://doaj.org/toc/1662-5137Alcohol withdrawal syndrome (AWS) is characterized by neuronal hyperexcitability, autonomic dysregulation, and severe negative emotion. The nucleus tractus solitarius (NTS) likely plays a prominent role in the neurological processes underlying these symptoms as it is the main viscerosensory nucleus in the brain. The NTS receives visceral interoceptive inputs, influences autonomic outputs, and has strong connections to the limbic system and hypothalamic-pituitary-adrenal axis to maintain homeostasis. Our prior analysis of single neuronal gene expression data from the NTS shows that neurons exist in heterogeneous transcriptional states that form distinct functional subphenotypes. Our working model conjectures that the allostasis secondary to alcohol dependence causes peripheral and central biological network decompensation in acute abstinence resulting in neurovisceral feedback to the NTS that substantially contributes to the observed AWS. We collected single noradrenergic and glucagon-like peptide-1 (GLP-1) neurons and microglia from rat NTS and measured a subset of their transcriptome as pooled samples in an alcohol withdrawal time series. Inflammatory subphenotypes predominate at certain time points, and GLP-1 subphenotypes demonstrated hyperexcitability post-withdrawal. We hypothesize such inflammatory and anxiogenic signaling contributes to alcohol dependence via negative reinforcement. Targets to mitigate such dysregulation and treat dependence can be identified from this dataset.Sean J. O’SullivanSean J. O’SullivanDamani McIntosh-ClarkeDamani McIntosh-ClarkeJames ParkJames ParkJames ParkRajanikanth VadigepalliRajanikanth VadigepalliJames S. SchwaberFrontiers Media S.A.articlealcohol withdrawalneuroinflammationRT-PCRsubphenotypessingle-cell heterogeneitymicrogliaNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Systems Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alcohol withdrawal neuroinflammation RT-PCR subphenotypes single-cell heterogeneity microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	alcohol withdrawal neuroinflammation RT-PCR subphenotypes single-cell heterogeneity microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Sean J. O’Sullivan Sean J. O’Sullivan Damani McIntosh-Clarke Damani McIntosh-Clarke James Park James Park James Park Rajanikanth Vadigepalli Rajanikanth Vadigepalli James S. Schwaber Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series
description	Alcohol withdrawal syndrome (AWS) is characterized by neuronal hyperexcitability, autonomic dysregulation, and severe negative emotion. The nucleus tractus solitarius (NTS) likely plays a prominent role in the neurological processes underlying these symptoms as it is the main viscerosensory nucleus in the brain. The NTS receives visceral interoceptive inputs, influences autonomic outputs, and has strong connections to the limbic system and hypothalamic-pituitary-adrenal axis to maintain homeostasis. Our prior analysis of single neuronal gene expression data from the NTS shows that neurons exist in heterogeneous transcriptional states that form distinct functional subphenotypes. Our working model conjectures that the allostasis secondary to alcohol dependence causes peripheral and central biological network decompensation in acute abstinence resulting in neurovisceral feedback to the NTS that substantially contributes to the observed AWS. We collected single noradrenergic and glucagon-like peptide-1 (GLP-1) neurons and microglia from rat NTS and measured a subset of their transcriptome as pooled samples in an alcohol withdrawal time series. Inflammatory subphenotypes predominate at certain time points, and GLP-1 subphenotypes demonstrated hyperexcitability post-withdrawal. We hypothesize such inflammatory and anxiogenic signaling contributes to alcohol dependence via negative reinforcement. Targets to mitigate such dysregulation and treat dependence can be identified from this dataset.
format	article
author	Sean J. O’Sullivan Sean J. O’Sullivan Damani McIntosh-Clarke Damani McIntosh-Clarke James Park James Park James Park Rajanikanth Vadigepalli Rajanikanth Vadigepalli James S. Schwaber
author_facet	Sean J. O’Sullivan Sean J. O’Sullivan Damani McIntosh-Clarke Damani McIntosh-Clarke James Park James Park James Park Rajanikanth Vadigepalli Rajanikanth Vadigepalli James S. Schwaber
author_sort	Sean J. O’Sullivan
title	Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series
title_short	Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series
title_full	Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series
title_fullStr	Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series
title_full_unstemmed	Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series
title_sort	single cell scale neuronal and glial gene expression and putative cell phenotypes and networks in the nucleus tractus solitarius in an alcohol withdrawal time series
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ee4e039aba274d2a8f26a523ce0f09d5
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Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series

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