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The central nucleus of the amygdala (CeA) plays a critical role in the development of alcohol dependence and escalation of alcohol consumption in dependent subjects. Molecular mechanisms underlying the CeA-driven behavioral changes are not well understood. Here, we examined the effects of alcohol on global gene expression in the CeA using a chronic intermittent ethanol (CIE) vapor model in rats and RNA sequencing (RNA-Seq). The CIE procedure resulted in robust changes in CeA gene expression during intoxication, as the number of differentially expressed genes (DEGs) was significantly greater than those expected by chance. Over-representation analysis of cell types, functional groups and molecular pathways revealed biological categories potentially important for the development of alcohol dependence in our model. Genes specific for astrocytes, myelinating oligodendrocytes, and endothelial cells were over-represented in the DEG category, suggesting that these cell types were particularly affected by the CIE procedure. The majority of the over-represented functional groups and molecular pathways were directly related to the functions of glial and endothelial cells, including extracellular matrix (ECM) organization, myelination, and the regulation of innate immune response. A coordinated regulation of several ECM metalloproteinases (e.g., Mmp2; Mmp14), their substrates (e.g., multiple collagen genes and myelin basic protein; Mbp), and a metalloproteinase inhibitor, Reck, suggests a specific mechanism for ECM re-organization in response to chronic alcohol, which may modulate neuronal activity and result in behavioral changes, such as an escalation of alcohol drinking. Our results highlight the importance of glial and endothelial cells in the effects of chronic alcohol exposure on the CeA, and demonstrate further insight into the molecular mechanisms of alcohol dependence in rats. These molecular targets may be used in future studies to develop therapeutics to treat AUD.<\/jats:p>","DOI":"10.3390\/brainsci11091149","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T21:45:16Z","timestamp":1630273516000},"page":"1149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Alcohol Dependence in Rats Is Associated with Global Changes in Gene Expression in the Central Amygdala"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-1190","authenticated-orcid":false,"given":"Brent R.","family":"Kisby","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas at Austin, Austin, TX 78715, USA"},{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"McManus","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence P.","family":"Varodayan","sequence":"additional","affiliation":[{"name":"Department of Psychology, Binghamton University-SUNY, Binghamton, NY 13902, USA"},{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Roberto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Adron","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas at Austin, Austin, TX 78715, USA"},{"name":"Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78741, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Ponomarev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,29]]},"reference":[{"key":"ref_1","unstructured":"American Psychiatric Association (2015). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1097\/01.ALC.0000145781.11923.4E","article-title":"Enhanced Alcohol Self-Administration after Intermittent versus Continuous Alcohol Vapor Exposure","volume":"28","author":"Roberts","year":"2004","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.alcohol.2008.07.001","article-title":"Neuropeptide Y Suppresses Ethanol Drinking in Ethanol-Abstinent, but Not Non-Ethanol-Abstinent, Wistar Rats","volume":"42","author":"Gilpin","year":"2008","journal-title":"Alcohol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.biopsych.2009.11.007","article-title":"Corticotropin Releasing Factor-Induced Amygdala Gamma-Aminobutyric Acid Release Plays a Key Role in Alcohol Dependence","volume":"67","author":"Roberto","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1523\/JNEUROSCI.3721-16.2017","article-title":"Alcohol Dependence Disrupts Amygdalar L-Type Voltage-Gated Calcium Channel Mechanisms","volume":"37","author":"Varodayan","year":"2017","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10729","DOI":"10.1523\/JNEUROSCI.1267-16.2016","article-title":"A Functional Switch in Tonic GABA Currents Alters the Output of Central Amygdala Corticotropin Releasing Factor Receptor-1 Neurons Following Chronic Ethanol Exposure","volume":"36","author":"Herman","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1097\/01.ALC.0000149977.95306.3A","article-title":"Increased Ethanol Drinking after Repeated Chronic Ethanol Exposure and Withdrawal Experience in C57BL\/6 Mice","volume":"28","author":"Becker","year":"2004","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1007\/s12035-018-1252-0","article-title":"Dissecting Brain Networks Underlying Alcohol Binge Drinking Using a Systems Genomics Approach","volume":"56","author":"Ferguson","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.celrep.2019.08.083","article-title":"Dissecting the Roles of GABA and Neuropeptides from Rat Central Amygdala CRF Neurons in Anxiety and Fear Learning","volume":"29","author":"Pomrenze","year":"2019","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.biopsych.2014.09.008","article-title":"The Central Amygdala as an Integrative Hub for Anxiety and Alcohol Use Disorders","volume":"77","author":"Gilpin","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbi.2014.03.007","article-title":"Innate Immune Factors Modulate Ethanol Interaction with GABAergic Transmission in Mouse Central Amygdala","volume":"40","author":"Bajo","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.biopsych.2013.03.014","article-title":"The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins\/Kappa-Opioid Receptors","volume":"75","author":"Kissler","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"a039339","DOI":"10.1101\/cshperspect.a039339","article-title":"The Role of the Central Amygdala in Alcohol Dependence","volume":"11","author":"Roberto","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neuropharm.2016.11.021","article-title":"Sex Differences in Responses of the Basolateral-Central Amygdala Circuit to Alcohol, Corticosterone and Their Interaction","volume":"114","author":"Logrip","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_15","first-page":"223","article-title":"GABA B Receptor Agonist Only Reduces Ethanol Drinking in Light-Drinking Mice","volume":"102","author":"Roberto","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7761","DOI":"10.1523\/JNEUROSCI.0483-18.2018","article-title":"Central Amygdala Circuits Mediate Hyperalgesia in Alcohol-Dependent Rats","volume":"38","author":"Avegno","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Agoglia, A.E., Zhu, M., Quadir, S.G., Bluitt, M.N., Douglass, E., Hanback, T., Tella, J., Ying, R., Hodge, C.W., and Herman, M.A. (2021). Sex-Specific Plasticity in CRF Regulation of Inhibitory Control in Central Amygdala CRF1 Neurons after Chronic Voluntary Alcohol Drinking. Addict. Biol., e13067.","DOI":"10.1111\/adb.13067"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108527","DOI":"10.1016\/j.neuropharm.2021.108527","article-title":"Repeated Binge Ethanol Drinking Enhances Electrical Activity of Central Amygdala Corticotropin Releasing Factor Neurons in Vivo","volume":"189","author":"Aroni","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of Addiction: A Neurocircuitry Analysis","volume":"3","author":"Koob","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/adb.12181","article-title":"Cell-Type-Specific Tonic GABA Signaling in the Rat Central Amygdala Is Selectively Altered by Acute and Chronic Ethanol","volume":"21","author":"Herman","year":"2016","journal-title":"Addict. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e14245","DOI":"10.14814\/phy2.14245","article-title":"Synaptic GABAergic Transmission in the Central Amygdala (CeA) of Rats Depends on Slice Preparation and Recording Conditions","volume":"7","author":"Avegno","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10159","DOI":"10.1523\/JNEUROSCI.3004-04.2004","article-title":"Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats","volume":"24","author":"Roberto","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1523\/JNEUROSCI.5077-03.2004","article-title":"Acute and Chronic Ethanol Alter Glutamatergic Transmission in Rat Central Amygdala: An In Vitro and In Vivo Analysis","volume":"24","author":"Roberto","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neuropharm.2017.07.017","article-title":"P\/Q-Type Voltage-Gated Calcium Channels Mediate the Ethanol and CRF Sensitivity of Central Amygdala GABAergic Synapses","volume":"125","author":"Varodayan","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.neubiorev.2011.11.002","article-title":"Neuropeptide Modulation of Central Amygdala Neuroplasticity Is a Key Mediator of Alcohol Dependence","volume":"36","author":"Gilpin","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a012195","DOI":"10.1101\/cshperspect.a012195","article-title":"The Central Amygdala and Alcohol: Role of \u03b3-Aminobutyric Acid, Glutamate, and Neuropeptides","volume":"2","author":"Roberto","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9446","DOI":"10.1523\/JNEUROSCI.1395-16.2016","article-title":"Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence","volume":"36","author":"Crawford","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101952","DOI":"10.1016\/j.pneurobio.2020.101952","article-title":"IL-10 Normalizes Aberrant Amygdala GABA Transmission and Reverses Anxiety-like Behavior and Dependence-Induced Escalation of Alcohol Intake","volume":"199","author":"Patel","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0402-20.2020","article-title":"Cell-Type Specificity of Neuronal Excitability and Morphology in the Central Amygdala","volume":"8","author":"Adke","year":"2021","journal-title":"eNeuro"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1152\/jn.00514.2012","article-title":"Morphology, PKC\u03b4 Expression, and Synaptic Responsiveness of Different Types of Rat Central Lateral Amygdala Neurons","volume":"108","author":"Amano","year":"2012","journal-title":"J. Neurophysiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.alcohol.2009.12.001","article-title":"Changes in Gene Expression in Regions of the Extended Amygdala of Alcohol-Preferring Rats after Binge-like Alcohol Drinking","volume":"44","author":"McBride","year":"2010","journal-title":"Alcohol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pbb.2013.12.009","article-title":"Changes in Gene Expression within the Extended Amygdala Following Binge-like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats","volume":"117","author":"McBride","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/npp.2017.301","article-title":"Genome-Wide Expression Profiles Drive Discovery of Novel Compounds That Reduce Binge Drinking in Mice","volume":"43","author":"Ferguson","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/mp.2014.159","article-title":"Transcriptome Organization for Chronic Alcohol Abuse in Human Brain","volume":"20","author":"Farris","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6368","DOI":"10.1073\/pnas.0510188103","article-title":"Toward Understanding the Genetics of Alcohol Drinking through Transcriptome Meta-Analysis","volume":"103","author":"Mulligan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1530-0277.2010.01384.x","article-title":"Molecular Profiles of Drinking Alcohol to Intoxication in C57BL\/6J Mice","volume":"35","author":"Mulligan","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/acer.12288","article-title":"Bioinformatics Analyses Reveal Age-Specific Neuroimmune Modulation as a Target for Treatment of High Ethanol Drinking","volume":"38","author":"Agrawal","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/adb.12501","article-title":"On the Relationships in Rhesus Macaques between Chronic Ethanol Consumption and the Brain Transcriptome","volume":"23","author":"Iancu","year":"2018","journal-title":"Addict. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/acer.14312","article-title":"RNA-Seq Analysis of Genetic and Transcriptome Network Effects of Dual-Trait Selection for Ethanol Preference and Withdrawal Using SOT and NOT Genetic Models","volume":"44","author":"Kozell","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3389\/fgene.2018.00300","article-title":"Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders","volume":"9","author":"Colville","year":"2018","journal-title":"Front. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5673","DOI":"10.1523\/JNEUROSCI.0860-06.2006","article-title":"Transcriptional Signatures of Cellular Plasticity in Mice Lacking the A1 Subunit of GABAA Receptors","volume":"26","author":"Ponomarev","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.alcohol.2016.09.001","article-title":"Genetic Divergence in the Transcriptional Engram of Chronic Alcohol Abuse: A Laser-Capture RNA-Seq Study of the Mouse Mesocorticolimbic System","volume":"58","author":"Mulligan","year":"2017","journal-title":"Alcohol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1111\/acer.13777","article-title":"Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs","volume":"42","author":"Iancu","year":"2018","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3389\/fnmol.2019.00197","article-title":"Cross-Species Co-Analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys","volume":"12","author":"Bogenpohl","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wolstenholme, J.T., Warner, J.A., Capparuccini, M.I., Archer, K.J., Shelton, K.L., and Miles, M.F. (2011). Genomic Analysis of Individual Differences in Ethanol Drinking: Evidence for Non-Genetic Factors in C57Bl\/6 Mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021100"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/gbb.12367","article-title":"Effects of Selection for Ethanol Preference on Gene Expression in the Nucleus Accumbens of HS-CC Mice","volume":"16","author":"Colville","year":"2017","journal-title":"Genes Brain Behav."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/gbb.12266","article-title":"Alcohol Consumption Induces Global Gene Expression Changes in VTA Dopaminergic Neurons","volume":"15","author":"Marballi","year":"2016","journal-title":"Genes Brain Behav."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pbb.2009.07.019","article-title":"Gene Expression Changes in the Nucleus Accumbens of Alcohol-Preferring Rats Following Chronic Ethanol Consumption","volume":"94","author":"Bell","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1523\/JNEUROSCI.2002-16.2016","article-title":"Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents","volume":"37","author":"Harris","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.alcohol.2015.03.001","article-title":"Applying the New Genomics to Alcohol Dependence","volume":"49","author":"Farris","year":"2015","journal-title":"Alcohol"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1523\/JNEUROSCI.3136-11.2012","article-title":"Gene Coexpression Networks in Human Brain Identify Epigenetic Modifications in Alcohol Dependence","volume":"32","author":"Ponomarev","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_52","first-page":"286","article-title":"Coordinated Dysregulation of MRNAs and MicroRNAs in the Rat Medial Prefrontal Cortex Following a History of Alcohol Dependence","volume":"13","author":"Tapocik","year":"2012","journal-title":"Pharm. J."},{"key":"ref_53","first-page":"1","article-title":"Identifying Candidate Drivers of Alcohol Dependence-Induced Excessive Drinking by Assembly and Interrogation of Brain-Specific Regulatory Networks","volume":"16","author":"Shin","year":"2015","journal-title":"Genome Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e13021","DOI":"10.1111\/adb.13021","article-title":"Effect of Chronic Ethanol Consumption in Rhesus Macaques on the Nucleus Accumbens Core Transcriptome","volume":"26","author":"Walter","year":"2021","journal-title":"Addict. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hitzemann, R., Bergeson, S.E., Berman, A.E., Bubier, J.A., Chesler, E.J., Finn, D.A., Hein, L., Hoffman, P., Holmes, A., and Kisby, B.R. (2021). Sex Differences in the Brain Transcriptome Related to Alcohol Effects and Alcohol Use Disorder. Biol. Psychiatry.","DOI":"10.1016\/j.biopsych.2021.04.016"},{"key":"ref_56","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Elsevier."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and Accurate Short Read Alignment with Burrows-Wheeler Transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","article-title":"An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex","volume":"34","author":"Zhang","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","article-title":"Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing","volume":"101","author":"Li","year":"2019","journal-title":"Neuron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bbi.2019.08.185","article-title":"Increased IL-6 Expression in Astrocytes Is Associated with Emotionality, Alterations in Central Amygdala GABAergic Transmission, and Excitability during Alcohol Withdrawal","volume":"82","author":"Roberts","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/164_2017_77","article-title":"Ethanol and Cytokines in the Central Nervous System","volume":"248","author":"Roberto","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.alcohol.2018.11.004","article-title":"The Influence of Central Interleukin-6 on Behavioral Changes Associated with Acute Alcohol Intoxication in Adult Male Rats","volume":"79","author":"Barney","year":"2019","journal-title":"Alcohol"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ferguson, L.B., Patil, S., Moskowitz, B.A., Ponomarev, I., Harris, R.A., Mayfield, R.D., and Messing, R.O. (2019). A Pathway-Based Genomic Approach to Identify Medications: Application to Alcohol Use Disorder. Brain Sci., 9.","DOI":"10.3390\/brainsci9120381"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e12715","DOI":"10.1111\/adb.12715","article-title":"The Role of Matrix Metalloproteinase-9 in Negative Reinforcement Learning and Plasticity in Alcohol Dependence","volume":"25","author":"Go","year":"2019","journal-title":"Addict. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1126\/science.1092550","article-title":"Ethanol Augments GABAergic Transmission in the Central Amygdala via CRF1 Receptors","volume":"303","author":"Nie","year":"2004","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1111\/adb.12289","article-title":"Effects of Chronic Alcohol Consumption on Neuronal Function in the Non-Human Primate BNST","volume":"21","author":"Pleil","year":"2016","journal-title":"Addict. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/s41386-018-0290-7","article-title":"Synaptic Adaptations in the Central Amygdala and Hypothalamic Paraventricular Nucleus Associated with Protracted Ethanol Abstinence in Male Rhesus Monkeys","volume":"44","author":"Jimenez","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gorini, G., Roberts, A.J., and Mayfield, R.D. (2013). Neurobiological Signatures of Alcohol Dependence Revealed by Protein Profiling. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082656"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e1800255","DOI":"10.1002\/bies.201800255","article-title":"Function and Mechanism of Myelin Regulation in Alcohol Abuse and Alcoholism","volume":"41","author":"Rice","year":"2019","journal-title":"BioEssays"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fnmol.2018.00078","article-title":"Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders","volume":"11","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1111\/acer.13200","article-title":"Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder","volume":"40","author":"Lasek","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbi.2018.12.006","article-title":"Toll-like Receptor 3 Dynamics in Female C57BL\/6J Mice: Regulation of Alcohol Intake","volume":"77","author":"Warden","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/adb.12539","article-title":"Chronic Ethanol Consumption: Role of TLR3\/TRIF-Dependent Signaling","volume":"23","author":"McCarthy","year":"2018","journal-title":"Addict. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.alcohol.2017.01.016","article-title":"Mechanistic Insights into Epigenetic Modulation of Ethanol Consumption","volume":"60","author":"Ponomarev","year":"2017","journal-title":"Alcohol"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10949","DOI":"10.1038\/s41598-019-47454-4","article-title":"Glial Gene Networks Associated with Alcohol Dependence","volume":"9","author":"Erickson","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.biopsych.2020.05.011","article-title":"Microglia Control Escalation of Drinking in Alcohol Dependent Mice: Genomic and Synaptic Drivers","volume":"88","author":"Warden","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e12889","DOI":"10.1111\/adb.12889","article-title":"Microglia Depletion and Alcohol: Transcriptome and Behavioral Profiles","volume":"26","author":"Warden","year":"2020","journal-title":"Addict. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41386-020-0721-0","article-title":"Cortical Astrocytes Regulate Ethanol Consumption and Intoxication in Mice","volume":"46","author":"Erickson","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1042\/CS20110340","article-title":"IL-6\/IL-6 Receptor System and Its Role in Physiological and Pathological Conditions","volume":"122","author":"Mihara","year":"2012","journal-title":"Clin. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2174\/0929867053363243","article-title":"Matrix Metalloproteinase Inhibitors: A Review on Pharmacophore Mapping and (Q)Sars Results","volume":"12","author":"Kontogiorgis","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-Endothelial Interactions at the Blood-Brain Barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/dneu.20974","article-title":"Extracellular Matrix and Perineuronal Nets in CNS Repair","volume":"71","author":"Kwok","year":"2011","journal-title":"Dev. Neurobiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1189\/jlb.0607338","article-title":"Chemokine and Cytokine Processing by Matrix Metalloproteinases and Its Effect on Leukocyte Migration and Inflammation","volume":"82","author":"Libert","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/j.bmc.2007.01.011","article-title":"Matrix Metalloproteinases (MMPs): Chemical-Biological Functions and (Q)SARs","volume":"15","author":"Verma","year":"2007","journal-title":"Bioorganic Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/acer.12239","article-title":"Alcohol Modulation of Cardiac Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of MMPs Favors Collagen Accumulation","volume":"38","author":"Voloshenyuk","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.biopsych.2016.12.026","article-title":"Archival Report Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking Behavior","volume":"81","author":"Stefaniuk","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/jnr.23288","article-title":"Membrane-Type 1 Metalloproteinase Is Upregulated in Microglia\/Brain Macrophages in Neurodegenerative and Neuroinflammatory Diseases","volume":"92","author":"Langenfurth","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1369\/0022155411401748","article-title":"Proteolytic Cleavage of Versican and Involvement of ADAMTS-1 in VEGF-A\/VPF-Induced Pathological Angiogenesis","volume":"59","author":"Fu","year":"2011","journal-title":"J. Histochem. Cytochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1523\/JNEUROSCI.20-21-07964.2000","article-title":"Tumor Necrosis Factor \u03b1 Induces a Metalloprotease-Disintegrin, ADAM8 (CD 156): Implications for Neuron-Glia Interactions during Neurodegeneration","volume":"20","author":"Schlomann","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_91","first-page":"881","article-title":"A Study of TNF Pathway Activation in Schizophrenia and Bipolar Disorder in Plasma and Brain Tissue","volume":"43","author":"Hoseth","year":"2017","journal-title":"Schizophr. Bull."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0092-8674(01)00597-9","article-title":"The Membrane-Anchored MMP Inhibitor RECK Is a Key Regulator of Extracellular Matrix Integrity and Angiogenesis","volume":"107","author":"Oh","year":"2001","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13221","DOI":"10.1073\/pnas.95.22.13221","article-title":"Regulation of Matrix Metalloproteinase-9 and Inhibition of Tumor Invasion by the Membrane-Anchored Glycoprotein RECK","volume":"95","author":"Takahashi","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1471-4159.2010.06933.x","article-title":"The Reck Tumor Suppressor Protein Alleviates Tissue Damage and Promotes Functional Recovery after Transient Cerebral Ischemia in Mice","volume":"115","author":"Wang","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1126\/science.1109418","article-title":"Mutations in Col4a1 Cause Perinatal Cerebral Hemorrhage and Porencephaly","volume":"308","author":"Gould","year":"2005","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/hmg\/ddp584","article-title":"Col4a1 Mutation in Mice Causes Defects in Vascular Function and Low Blood Pressure Associated with Reduced Red Blood Cell Volume","volume":"19","author":"Bailey","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.yjmcc.2016.04.010","article-title":"Exposure to Chronic Alcohol Accelerates Development of Wall Stress and Eccentric Remodeling in Rats with Volume Overload","volume":"97","author":"Mouton","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2174\/1389202911314020003","article-title":"Integrated Analysis of Transcriptomic and Proteomic Data","volume":"14","author":"Haider","year":"2013","journal-title":"Curr. Genom."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1002\/pmic.201000327","article-title":"Protein Abundances Are More Conserved than MRNA Abundances across Diverse Taxa","volume":"10","author":"Laurent","year":"2010","journal-title":"Proteomics"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Perl, K., Ushakov, K., Pozniak, Y., Yizhar-Barnea, O., Bhonker, Y., Shivatzki, S., Geiger, T., Avraham, K.B., and Shamir, R. (2017). Reduced Changes in Protein Compared to MRNA Levels across Non-Proliferating Tissues. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3683-9"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1530-0277.2011.01610.x","article-title":"Corticotropin-Releasing Factor Acting on Corticotropin-Releasing Factor Receptor Type 1 Is Critical for Binge Alcohol Drinking in Mice","volume":"36","author":"Kaur","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.biopsych.2016.02.029","article-title":"Extended Amygdala to Ventral Tegmental Area Corticotropin-Releasing Factor Circuit Controls Binge Ethanol Intake","volume":"81","author":"Rinker","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1038\/npp.2016.44","article-title":"Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala","volume":"41","author":"Itoga","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1111\/acer.12825","article-title":"Corticotropin Releasing Factor Binding Protein and CRF2 Receptors in the Ventral Tegmental Area: Modulation of Ethanol Binge Drinking in C57BL\/6J Mice","volume":"39","author":"Hwa","year":"2015","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e953","DOI":"10.1038\/tp.2016.208","article-title":"Defining the Role of Corticotropin Releasing Factor Binding Protein in Alcohol Consumption","volume":"6","author":"Henry","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1111\/acer.13119","article-title":"Binge Drinking Decreases Corticotropin-Releasing Factor-Binding Protein Expression in the Medial Prefrontal Cortex of Mice","volume":"40","author":"Ketchesin","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/9\/1149\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:54:52Z","timestamp":1760165692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/9\/1149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,29]]},"references-count":106,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["brainsci11091149"],"URL":"https:\/\/doi.org\/10.3390\/brainsci11091149","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,29]]}}}