Alcohol vapor exposure differentially impacts mesocorticolimbic cytokine expression in a sex-, region-, and duration-specific manner

Baxter-Potter, Lydia N.; Henricks, Angela M.; Berger, Anthony L.; Lugo, Janelle M.; McLaughlin, Ryan J.

doi:10.1016/j.neuroscience.2017.01.015

Cited by 25 publications

(15 citation statements)

References 63 publications

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“…The CIE protocol described in the present study is routinely implemented to mimic the high BACs regularly achieved in humans, and results in physiological neuroadaptations that facilitate severe alcohol dependence 124,125 . Another commonly used animal model of alcohol abuse is a voluntary, chronic every-other-day drinking paradigm (EOD), which causes escalated alcohol consumption over time, but not severe alcohol dependence 126,127 .…”

Section: Resultsmentioning

confidence: 99%

Glial gene networks associated with alcohol dependence

Erickson

Blednov

Harris

2019

Sci Rep

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Chronic alcohol abuse alters the molecular structure and function of brain cells. Recent work suggests adaptations made by glial cells, such as astrocytes and microglia, regulate physiological and behavioral changes associated with addiction. Defining how alcohol dependence alters the transcriptome of different cell types is critical for developing the mechanistic hypotheses necessary for a nuanced understanding of cellular signaling in the alcohol-dependent brain. We performed RNA-sequencing on total homogenate and glial cell populations isolated from mouse prefrontal cortex (PFC) following chronic intermittent ethanol vapor exposure (CIE). Compared with total homogenate, we observed unique and robust gene expression changes in astrocytes and microglia in response to CIE. Gene co-expression network analysis revealed biological pathways and hub genes associated with CIE in astrocytes and microglia that may regulate alcohol-dependent phenotypes. Astrocyte identity and synaptic calcium signaling genes were enriched in alcohol-associated astrocyte networks, while TGF-β signaling and inflammatory response genes were disrupted by CIE treatment in microglia gene networks. Genes related to innate immune signaling, specifically interferon pathways, were consistently up-regulated across CIE-exposed astrocytes, microglia, and total homogenate PFC tissue. This study illuminates the cell-specific effects of chronic alcohol exposure and provides novel molecular targets for studying alcohol dependence.

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Section: Resultsmentioning

confidence: 99%

Glial gene networks associated with alcohol dependence

Erickson

Blednov

Harris

2019

Sci Rep

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“…Moreover, the current findings are also in line with several neural cue‐reactivity studies in nicotine dependence (Cosgrove et al., ; Dumais et al., ). Animal studies have also reported that acute and chronic alcohol exposure only alters striatal mRNA expression in male, but not in female rats (Baxter‐Potter et al., ) and that there is a differential involvement of serotonergic and noradrenergic signalling in cue‐induced reinstatement (Kohtz & Aston‐Jones, ). Altogether, the current study supports the hypothesis that different (neural) mechanisms may underlie the development and persistence of substance use disorders in males and females.…”

Section: Discussionmentioning

confidence: 99%

Striatal alcohol cue‐reactivity is stronger in male than female problem drinkers

Kaag

Wiers

Vries

et al. 2018

Eur J of Neuroscience

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Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue-reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue-reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity.

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“…Alcohol withdrawal increases brain neuroimmune proteins such as chemokine C-C motif ligand 2 (CCL2; He and Crews, 2008;Ehrlich et al, 2012;Freeman et al, 2012;Vetreno et al, 2013;Whitman et al, 2013;Kane et al, 2014;Harper et al, 2015) in a brain-region-specific fashion (Knapp et al, 2016;Baxter-Potter et al, 2017). Given that chemokines like CCL2 are thought to act as neuromodulators (Adler et al, 2006;Gruol, 2016), it has been suggested that CCL2 and similar chemokines can alter alcohol withdrawal-related behaviors.…”

Section: Introductionmentioning

confidence: 99%

Phenotyping CCL2 Containing Central Amygdala Neurons Controlling Alcohol Withdrawal-Induced Anxiety

Harper

Knapp

Todd

et al. 2020

Front. Cell. Neurosci.

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Chemokines such as chemokine (C-C motif) ligand 2 (CCL2) play a role in several behaviors, including anxiety-like behavior, but whether neurons are an important source of CCL2 for behavior and how neuronal CCL2 may work to affect behavior are still debated. When a herpes simplex virus (HSV) vector was used to knockdown CCL2 mRNA in neurons of the central nucleus of the amygdala (CeA) in rats experiencing multiple withdrawals from low dose ethanol, anxiety-like behavior appeared in the social interaction task. To examine this finding further Fractalkine (CX3CL1), a chemokine that is often found to have an opposing function to CCL2 was measured in these rats. Both alcohol withdrawal and CCL2 knockdown increased the levels of the anti-inflammatory protein CX3CL1. The combination of alcohol withdrawal and CCL2 knockdown decreased CX3CL1 and may alter pro-inflammatory/anti-inflammatory balance, and thus highlights the potential importance of CCL2 and CCL2/CX3CL1 balance in anxiety. To find a mechanism by which neuronal chemokines like CCL2 could affect behavior, retrograde tracing with fluorescent nanobeads was done in two brain regions associated with anxiety the bed nucleus of the stria terminalis (BNST) and the ventral periaqueductal gray (VPAG). These studies identified CeA projection neurons to these brain regions that contain CCL2. To demonstrate that CCL2 can be transported via axons to downstream brain regions, the axonal transport blocker, colchicine, was given and 24 h later, the accumulation of CCL2 in CeA neuronal cell bodies was found. Finally, CCL2 in CeA neurons was localized to the synapse using confocal microscopy with enhanced resolution following deconvolution and electron microscopy, which along with the other evidence suggests that CCL2 may be transported down axons in CeA neurons and released from nerve terminals perhaps into brain regions like the BNST and VPAG to affect behaviors such as anxiety. These results suggest that neurons are an important target for chemokine research related to behavior.

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Alcohol vapor exposure differentially impacts mesocorticolimbic cytokine expression in a sex-, region-, and duration-specific manner

Cited by 25 publications

References 63 publications

Glial gene networks associated with alcohol dependence

Glial gene networks associated with alcohol dependence

Striatal alcohol cue‐reactivity is stronger in male than female problem drinkers

Phenotyping CCL2 Containing Central Amygdala Neurons Controlling Alcohol Withdrawal-Induced Anxiety

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