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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Systems Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnsys.2021.739790/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T23:27:35Z |
| format | Article |
| id | doaj.art-ee4e039aba274d2a8f26a523ce0f09d5 |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-12-20T23:27:35Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-ee4e039aba274d2a8f26a523ce0f09d52022-12-21T19:23:21ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372021-11-011510.3389/fnsys.2021.739790739790Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time SeriesSean J. O’Sullivan0Sean J. O’Sullivan1Damani McIntosh-Clarke2Damani McIntosh-Clarke3James Park4James Park5James Park6Rajanikanth Vadigepalli7Rajanikanth Vadigepalli8James S. Schwaber9Department of Pathology, Anatomy, and Cell Biology, Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United StatesBrain Stimulation Lab, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Anatomy, and Cell Biology, Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Pathology, Anatomy, and Cell Biology, Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Chemical Engineering, University of Delaware, Newark, DE, United StatesInstitute for Systems Biology, Seattle, WA, United StatesDepartment of Pathology, Anatomy, and Cell Biology, Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Chemical Engineering, University of Delaware, Newark, DE, United StatesDepartment of Pathology, Anatomy, and Cell Biology, Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United StatesAlcohol 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.https://www.frontiersin.org/articles/10.3389/fnsys.2021.739790/fullalcohol withdrawalneuroinflammationRT-PCRsubphenotypessingle-cell heterogeneitymicroglia |
| spellingShingle | 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 Frontiers in Systems Neuroscience alcohol withdrawal neuroinflammation RT-PCR subphenotypes single-cell heterogeneity microglia |
| 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_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_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_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 |
| topic | alcohol withdrawal neuroinflammation RT-PCR subphenotypes single-cell heterogeneity microglia |
| url | https://www.frontiersin.org/articles/10.3389/fnsys.2021.739790/full |
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