Zahr NM, Pfefferbaum A. Alcohol’s effects on the brain: neuroimaging results in humans and animal models. Alcohol Research: Current Reviews; 2017.

Pfefferbaum A, Rosenbloom MJ, Fama R, Sassoon SA, Sullivan EV. Transcallosal white matter degradation detected with quantitative fiber tracking in alcoholic men and women: selective relations to dissociable functions. Alcohol Clin Exp Res. 2010;34(7):1201–11.

PubMed  PubMed Central  Google Scholar 

Alfonso-Loeches S, Pascual M, Gomez-Pinedo U, Pascual-Lucas M, Renau-Piqueras J, Guerri C. Toll-like receptor 4 participates in the myelin disruptions associated with chronic alcohol abuse. Glia. 2012;60(6):948–64.

PubMed  Google Scholar 

Lewohl JM, Wang L, Miles MF, Zhang L, Dodd PR, Harris RA. Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin Exp Res. 2000;24(12):1873–82.

CAS  PubMed  Google Scholar 

Mayfield RD, Lewohl JM, Dodd PR, Herlihy A, Liu J, Harris RA. Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics. J Neurochem. 2002;81(4):802–13.

CAS  PubMed  Google Scholar 

Putzke J, De Beun R, Schreiber R, De Vry J, Tolle TR, Zieglgansberger W, et al. Long-term alcohol self-administration and alcohol withdrawal differentially modulate microtubule-associated protein 2 (MAP2) gene expression in the rat brain. Brain Res Mol Brain Res. 1998;62(2):196–205.

CAS  PubMed  Google Scholar 

Paula-Barbosa MM, Tavares MA. Long term alcohol consumption induces microtubular changes in the adult rat cerebellar cortex. Brain Res. 1985;339(1):195–9.

CAS  PubMed  Google Scholar 

Pascual M, Montesinos J, Guerri C. Role of the innate immune system in the neuropathological consequences induced by adolescent binge drinking. J Neurosci Res. 2018;96(5):765–80.

CAS  PubMed  Google Scholar 

Montesinos J, Pascual M, Pla A, Maldonado C, Rodriguez-Arias M, Minarro J, et al. TLR4 elimination prevents synaptic and myelin alterations and long-term cognitive dysfunctions in adolescent mice with intermittent ethanol treatment. Brain Behav Immun. 2015;45:233–44.

CAS  PubMed  Google Scholar 

Montesinos J, Pascual M, Rodriguez-Arias M, Minarro J, Guerri C. Involvement of TLR4 in the long-term epigenetic changes, rewarding and anxiety effects induced by intermittent ethanol treatment in adolescence. Brain Behav Immun. 2016;53:159–71.

CAS  PubMed  Google Scholar 

Pandey SC, Sakharkar AJ, Tang L, Zhang H. Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. Neurobiol Dis. 2015;82:607–19.

CAS  PubMed  PubMed Central  Google Scholar 

Van Skike CE, Diaz-Granados JL, Matthews DB. Chronic intermittent ethanol exposure produces persistent anxiety in adolescent and adult rats. Alcohol Clin Exp Res 2015;39(2):262–271.

Crews FT, Vetreno RP. Mechanisms of neuroimmune gene induction in alcoholism. Psychopharmacology. 2016;233(9):1543–57.

CAS  PubMed  Google Scholar 

Szabo G, Saha B. Alcohol’s effect on host defense. Alcohol Res. 2015;37(2):159–70.

PubMed  PubMed Central  Google Scholar 

Lampron A, Elali A, Rivest S. Innate immunity in the CNS: redefining the relationship between the CNS and Its environment. Neuron. 2013;78(2):214–32.

CAS  PubMed  Google Scholar 

Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol. 2001;2(8):675–80.

CAS  PubMed  Google Scholar 

Dantzer R. Neuroimmune Interactions: from the brain to the immune system and vice versa. Physiol Rev. 2018;98(1):477–504.

CAS  PubMed  Google Scholar 

Lian H, Zheng H. Signaling pathways regulating neuron-glia interaction and their implications in Alzheimer’s disease. J Neurochem. 2016;136(3):475–91.

CAS  PubMed  Google Scholar 

Boulanger LM. Immune proteins in brain development and synaptic plasticity. Neuron. 2009;64(1):93–109.

CAS  PubMed  Google Scholar 

Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun. 2011;25(2):181–213.

CAS  PubMed  Google Scholar 

Niranjan R. Recent advances in the mechanisms of neuroinflammation and their roles in neurodegeneration. Neurochem Int. 2018;120:13–20.

CAS  PubMed  Google Scholar 

Brites D, Fernandes A. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci. 2015;9:476.

PubMed  PubMed Central  Google Scholar 

Kohno M, Link J, Dennis LE, McCready H, Huckans M, Hoffman WF, et al. Neuroinflammation in addiction: a review of neuroimaging studies and potential immunotherapies. Pharmacol Biochem Behav. 2019;179:34–42.

CAS  PubMed  PubMed Central  Google Scholar 

Montesinos J, Alfonso-Loeches S, Guerri C. Impact of the innate immune response in the actions of ethanol on the central nervous system. Alcohol Clin Exp Res. 2016;40(11):2260–70.

CAS  PubMed  Google Scholar 

Crews FT, Sarkar DK, Qin L, Zou J, Boyadjieva N, Vetreno RP. Neuroimmune function and the consequences of alcohol exposure. Alcohol Res. 2015;37(2):331–41 44–51.

PubMed  PubMed Central  Google Scholar 

Mayfield J, Ferguson L, Harris RA. Neuroimmune signaling: a key component of alcohol abuse. Curr Opin Neurobiol. 2013;23(4):513–20.

CAS  PubMed  PubMed Central  Google Scholar 

Roberto M, Patel RR, Bajo M. Ethanol and cytokines in the central nervous system. Handb Exp Pharmacol. 2018;248:397–431.

PubMed  Google Scholar 

Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21(7):677–87.

PubMed  PubMed Central  Google Scholar 

Dolasia K, Bisht MK, Pradhan G, Udgata A, Mukhopadhyay S. TLRs/NLRs: shaping the landscape of host immunity. Int Rev Immunol. 2018;37(1):3–19.

CAS  PubMed  Google Scholar 

Blanco AM, Perez-Arago A, Fernandez-Lizarbe S, Guerri C. Ethanol mimics ligand-mediated activation and endocytosis of IL-1RI/TLR4 receptors via lipid rafts caveolae in astroglial cells. J Neurochem. 2008;106(2):625–39.

CAS  PubMed  Google Scholar 

Blanco AM, Valles SL, Pascual M, Guerri C. Involvement of TLR4/type I IL-1 receptor signaling in the induction of inflammatory mediators and cell death induced by ethanol in cultured astrocytes. J Immunol. 2005;175(10):6893–9.

CAS  PubMed  Google Scholar 

Fernandez-Lizarbe S, Pascual M, Guerri C. Critical role of TLR4 response in the activation of microglia induced by ethanol. J Immunol. 2009;183(7):4733–44.

CAS  PubMed  Google Scholar 

Pascual-Lucas M, Fernandez-Lizarbe S, Montesinos J, Guerri C. LPS or ethanol triggers clathrin- and rafts/caveolae-dependent endocytosis of TLR4 in cortical astrocytes. J Neurochem. 2014;129(3):448–62.

CAS  PubMed  Google Scholar 

Alfonso-Loeches S, Pascual-Lucas M, Blanco AM, Sanchez-Vera I, Guerri C. Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage. J Neurosci. 2010;30(24):8285–95.

CAS  PubMed  PubMed Central  Google Scholar 

Alfonso-Loeches S, Urena-Peralta J, Morillo-Bargues MJ, Gomez-Pinedo U, Guerri C. Ethanol-induced TLR4/NLRP3 neuroinflammatory response in microglial cells promotes leukocyte infiltration across the BBB. Neurochem Res. 2016;41(1–2):193–209.

CAS  PubMed  Google Scholar 

Alfonso-Loeches S, Urena-Peralta JR, Morillo-Bargues MJ, Oliver-De La Cruz J, Guerri C. Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. Front Cell Neurosci 2014;8:216.

Warden AS, Azzam M, DaCosta A, Mason S, Blednov YA, Messing RO, et al. Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice. Brain Behav Immun. 2019;77:55–65.

CAS  PubMed  Google Scholar 

Su W, Aloi MS, Garden GA. MicroRNAs mediating CNS inflammation: small regulators with powerful potential. Brain Behav Immun. 2016;52:1–8.

PubMed  Google Scholar 

Lewohl JM, Nunez YO, Dodd PR, Tiwari GR, Harris RA, Mayfield RD. Up-regulation of microRNAs in brain of human alcoholics. Alcohol Clin Exp Res. 2011;35(11):1928–37.

CAS  PubMed  PubMed Central  Google Scholar 

Nunez YO, Mayfield RD. Understanding alcoholism through microRNA signatures in brains of human alcoholics. Front Genet. 2012;3:43.

CAS  PubMed  PubMed Central  Google Scholar 

Nunez YO, Truitt JM, Gorini G, Ponomareva ON, Blednov YA, Harris RA, et al. Positively correlated miRNA-mRNA regulatory networks in mouse frontal cortex during early stages of alcohol dependence. BMC Genomics. 2013;14:725.

CAS  PubMed  PubMed Central  Google Scholar 

Lippai D, Bala S, Csak T, Kurt-Jones EA, Szabo G. Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice. PLoS One. 2013;8(8):e70945.

CAS  PubMed  PubMed Central  Google Scholar 

Ramirez SH, Andrews AM, Paul D, Pachter JS. Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers. Fluids Barriers CNS. 2018;15(1):19.

PubMed  PubMed Central  Google Scholar 

Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 Cell. 1993;75(5):843–54.

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.

CAS  PubMed  PubMed Central  Google Scholar 

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73.

CAS  PubMed  Google Scholar 

Felekkis K, Touvana E, Stefanou C, Deltas C. microRNAs: a newly de