Alcohol and IL-6 Alter Expression of Synaptic Proteins in Cerebellum of Transgenic Mice with Increased Astrocyte Expression of IL-6

Gruol, Donna L.; Melkonian, Claudia; Ly, Kristine; Sisouvanthong, Jasmin; Tan, Yvette; Roberts, Amanda J.

doi:10.1016/j.neuroscience.2020.06.043

Cited by 6 publications

(5 citation statements)

References 127 publications

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“… References: T1: Koo and Duman, 2008 ; T2: Goshen et al, 2008 ; T3: Gajtko et al, 2020 ; T4: Spulber and Schultzberg, 2010 ; T5: Takemiya et al, 2017 ; T6: Clausen et al, 2011 ; T7: Sugama et al, 2011 ; T8: Spulber et al, 2011 ; T9: Liu et al, 2021 ; T10: Liu et al, 2013 ; T11: Viviani et al, 2006 ; T12: Zhu et al, 2006 ; T13: Lai et al, 2006 ; T14: Zhang et al, 2021 ; T15: Tong et al, 2012 ; T16: Patterson, 2015 ; T17: Rage et al, 2006 ; T18: Barrientos et al, 2004 ; T19: Jones et al, 2018 ; T20: Herrera et al, 2019 ; T21: Mai et al, 2019 ; T22: Fleshner et al, 1995 ; T23: Kai et al, 2021 ; T24: Harden et al, 2011 ; T25: Aniszewska et al, 2015 ; T26: Burton et al, 2011 ; T27: Gruol, 2015 ; T28: Sallmann et al, 2000 ; T29: Brown et al, 2014 ; T30: Yang et al, 2017 ; T31: Spooren et al, 2011 ; T32: Streit et al, 2000 ; T33: Schwieler et al, 2015 ; T34: Erta et al, 2012 ; T35: Gruol et al, 2020 ; T36: Hernandez et al, 2016 ; T37: Strle et al, 2001 ; T38: Perez-Asensio et al, 2013 ; T39: Sawada et al, 1999 ; T40: Laffer et al, 2019 ; T41: Balasingam and Yong, 1996 ; T42: Kvaratskhelia et al, 2009 ; T43: Zhou et al, 2009 ; T44: Burmeister and Marriott, 2018 ; T45: Lobo-Silva et al, 2016 ; T46: Kelly et al, 2001 ; T47: Nenov et al, 2019 ; T48: Ledeboer et al, 2000 ; T49: Molina-H...…”

Section: Cytokines and Kynureninesunclassified

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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Two of the molecular families closely associated with mediating communication between the brain and immune system are cytokines and the kynurenine metabolites of tryptophan. Both groups regulate neuron and glial activity in the central nervous system (CNS) and leukocyte function in the immune system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that the two families perform complementary functions generating an integrated network. The kynurenine pathway determines overall neuronal excitability and plasticity by modulating glutamate receptors and GPR35 activity across the CNS, and regulates general features of immune cell status, surveillance and tolerance which often involves the Aryl Hydrocarbon Receptor (AHR). Equally, cytokines and chemokines define and regulate specific populations of neurons, glia or immune system leukocytes, generating more specific responses within restricted CNS regions or leukocyte populations. In addition, as there is a much larger variety of these compounds, their homing properties enable the superimposition of dynamic variations of cell activity upon local, spatially limited, cell populations. This would in principle allow the targeting of potential treatments to restricted regions of the CNS. The proposed synergistic interface of ‘tonic’ kynurenine pathway affecting baseline activity and the superimposed ‘phasic’ cytokine system would constitute an integrated network explaining some features of neuroimmune communication. The concept would broaden the scope for the development of new treatments for disorders involving both the CNS and immune systems, with safer and more effective agents targeted to specific CNS regions.

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Section: Cytokines and Kynureninesunclassified

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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“…Our previous studies showed that CIE/withdrawal (i.e., no 2BC) altered the levels of IL-6, IL-6 signal transduction partners, and several synaptic proteins compared to alcohol-naïve control mice in the hippocampus and cerebellum when measurements were made 24 h after termination of CIE [ 27 , 30 , 81 ]. In the current studies, animals were sacrificed nine days after the cessation of 2BC and 2BC-CIE exposure.…”

Section: Resultsmentioning

confidence: 99%

“…The results are summarized in Table 4, along with results from our previous studies for comparison purposes. ↓ = significantly lower, ↑ = significantly higher, ns = relationship not significant, -= not determined, 1 data from [30,50,66], 2 data from [30], 3 data from [27,81].…”

Section: Effects Of 2bc and 2bc-cie On Inhibitory And Excitatory Syna...mentioning

confidence: 99%

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Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure

Gruol,

Calderon,

Huitron-Resendiz

et al. 2023

Cells

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Alcohol consumption activates the neuroimmune system of the brain, a system in which brain astrocytes and microglia play dominant roles. These glial cells normally produce low levels of neuroimmune factors, which are important signaling factors and regulators of brain function. Alcohol activation of the neuroimmune system is known to dysregulate the production of neuroimmune factors, such as the cytokine IL-6, thereby changing the neuroimmune status of the brain, which could impact the actions of alcohol. The consequences of neuroimmune–alcohol interactions are not fully known. In the current studies we investigated this issue in transgenic (TG) mice with altered neuroimmune status relative to IL-6. The TG mice express elevated levels of astrocyte-produced IL-6, a condition known to occur with alcohol exposure. Standard behavioral tests of alcohol drinking and negative affect/emotionality were carried out in homozygous and heterozygous TG mice and control mice to assess the impact of neuroimmune status on the actions of chronic intermittent alcohol (ethanol) (CIE) exposure on these behaviors. The expressions of signal transduction and synaptic proteins were also assessed by Western blot to identify the impact of alcohol–neuroimmune interactions on brain neurochemistry. The results from these studies show that neuroimmune status with respect to IL-6 significantly impacts the effects of alcohol on multiple levels.

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“…Alcohol withdrawal also increases the permeability of mitochondria to Ca+2 influx and increases the opening of the nonspecific permeability transition pore, which causes efflux of mitochondrial signals that induce neuron death ( Rewal et al, 2005 ). At the same time, alcohol reduces the expression of inhibitory GABAA receptors, glutamic acid decarboxylase, which catalyzes the metabolism of glutamate to GABA ( Proudfoot and Wilkins, 2017 ), and the protein that promotes GABA uptake into synaptic vesicles ( Gruol et al, 2020 ), further pushing the signaling balance toward a hyperexcitatory state. Interestingly, the actions of alcohol that evoke glutamate excitotoxicity differentiate alcohol-induced cerebellar ataxia from many other forms, which have been shown to depend on glutamate excitotoxicity through a deficiency in the expression of glutamic acid decarboxylase, which catalyzes the metabolism of glutamate to GABA ( Proudfoot and Wilkins, 2017 ).…”

Section: Putative Roles Of Alcohol In Specific Rare Neurodegenerative Diseasesmentioning

confidence: 99%

Impact of Alcohol Abuse on Susceptibility to Rare Neurodegenerative Diseases

Araujo

Henriksen

Gamsby

et al. 2021

Front. Mol. Biosci.

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Despite the prevalence and well-recognized adverse effects of prenatal alcohol exposure and alcohol use disorder in the causation of numerous diseases, their potential roles in the etiology of neurodegenerative diseases remain poorly characterized. This is especially true of the rare neurodegenerative diseases, for which small population sizes make it difficult to conduct broad studies of specific etiological factors. Nonetheless, alcohol has potent and long-lasting effects on neurodegenerative substrates, at both the cellular and systems levels. This review highlights the general effects of alcohol in the brain that contribute to neurodegeneration across diseases, and then focuses on specific diseases in which alcohol exposure is likely to play a major role. These specific diseases include dementias (alcohol-induced, frontotemporal, and Korsakoff syndrome), ataxias (cerebellar and frontal), and Niemann-Pick disease (primarily a Type B variant and Type C). We conclude that there is ample evidence to support a role of alcohol abuse in the etiology of these diseases, but more work is needed to identify the primary mechanisms of alcohol’s effects.

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Alcohol and IL-6 Alter Expression of Synaptic Proteins in Cerebellum of Transgenic Mice with Increased Astrocyte Expression of IL-6

Cited by 6 publications

References 127 publications

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure

Impact of Alcohol Abuse on Susceptibility to Rare Neurodegenerative Diseases

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