The neuroimmune system – Where aging and excess alcohol intersect

Carlson, Erika R.; Guerin, Steven; Nixon, Kimberly

doi:10.1016/j.alcohol.2022.08.009

Cited by 10 publications

(4 citation statements)

References 227 publications

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“…In addition to cytokines and microglial cells, astrocytes have also been reported to be critical regulators of alcohol intake ( Carlson et al, 2023 ; Miguel-Hidalgo, 2018 ; Adermark and Bowers, 2016 ). Astrocytes participate in the regulation of innate and adaptive immune responses in the brain ( Colombo and Farina, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent factors of alcohol and neuroimmune mechanisms

Cruz,

Borgonetti,

Bajo

et al. 2023

Neurobiology of Stress

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Section: Introductionmentioning

confidence: 99%

Sex-dependent factors of alcohol and neuroimmune mechanisms

Cruz,

Borgonetti,

Bajo

et al. 2023

Neurobiology of Stress

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“…The chronic activation of the neuroimmune system and elevated levels of neuroimmune factors are characteristic of alcohol use disorders (AUD) and other CNS conditions that are associated with impaired brain function such as neurodegenerative diseases, major depression, maladaptive stress responses, neuropsychiatric disorders, autism, injury, and even aging [ 1 , 2 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Some of these conditions are often co-morbid with AUD.…”

Section: Introductionmentioning

confidence: 99%

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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“…Microglia also react to insults such as those achieved with binge-like ethanol administration (see Melbourne et al, 2021 for review). For example, postmortem analysis of brains from humans with an AUD have shown reactive microglia ( He and Crews, 2008 ) and this effect may be age dependent ( Carlson et al, 2023 ). We have shown that alcohol exposure during adolescence causes a microglia reaction ( McClain et al, 2011 ; Peng and Nixon, 2021 ) that persists at least a month if not several months according to our adult models ( Obernier et al, 2002 ; Nixon et al, 2008 ; see also Melbourne et al, 2021 for review).…”

Section: Introductionmentioning

confidence: 99%

“…[ 3 H]PK11195 binding has been a highly sensitive indicator of microglia effects in alcohol models ( Marshall et al, 2013 ; Tyler et al, 2019 ) and one that persists at least months after alcohol exposure ( Obernier et al, 2002 ). Therefore, we chose this approach to increase our likelihood of detecting long-term effects in brain tissue as microglia reactivity increases with aging, neurodegeneration, and excessive alcohol use ( Carlson et al, 2023 ). Accordingly, [ 3 H]PK11195 was examined in three brain regions important for spatial learning (entorhinal cortex, dentate gyrus, and CA1 region of the hippocampus) from female and male ethanol treated animals.…”

Section: Introductionmentioning

confidence: 99%

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life

Matthews,

Scaletty,

Trapp

et al. 2023

Front. Behav. Neurosci.

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Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [3H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [3H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.

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The neuroimmune system – Where aging and excess alcohol intersect

Cited by 10 publications

References 227 publications

Sex-dependent factors of alcohol and neuroimmune mechanisms

Sex-dependent factors of alcohol and neuroimmune mechanisms

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

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life

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