Dataset Information

Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer.

ABSTRACT: Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in mice (1.0 mL of 1.5% or 5.0% ethanol (v/v) per day per mouse, up to 10 weeks) resulted in the elevation of colonic levels of oxidative stress markers (such as 8-hydroxy-2'-deoxyguanosine and 4-hydroxynonenal) compared to control mice, and this was consistently accompanied by elevated levels of inflammation-associated cytokines and immune cells (Th17 and macrophages) and a decreased level of regulatory T (Treg) cells to produce colonic lesions. It also resulted in an alteration of mouse fecal microbiota structures, reminiscent of the alterations observed in human inflammatory bowel disease, and this appeared to be consistent with the proposed sustained generation of oxidative stress in the colonic environment during chronic ethanol consumption. Moreover, the first experimental evidence that chronic ethanol administration results in elevated levels of advanced glycation end products (AGEs) and their receptors (RAGE) in the colonic tissues in mice is also shown, implying enhanced RAGE-mediated signaling with chronic ethanol administration. The RAGE-mediated signaling pathway has thus far been implicated as a link between the accumulation of AGEs and the development of many types of chronic colitis and cancers. Thus, enhancement of this pathway likely exacerbates the ethanol-induced inflammatory states of colonic tissues and might at least partly contribute to the pathogenesis of ER-CRC.

SUBMITTER: Ohira H

PROVIDER: S-EPMC7880462 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer.

Ohira Hideo H Tsuruya Atsuki A Oikawa Daiki D Nakagawa Wao W Mamoto Rie R Hattori Masahira M Waki Toshiyuki T Takahashi Seiji S Fujioka Yoshio Y Nakayama Toru T

PloS one 20210212 2

Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in m ...[more]

PMID: 33577585

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Project description:BackgroundA clinical hallmark of alcohol use disorder is persistent drinking despite potential adverse consequences. The ventromedial prefrontal cortex (vmPFC) and dorsomedial prefrontal cortex (dmPFC) are positioned to exert top-down control over subcortical regions, such as the nucleus accumbens shell (NAcS) and basolateral amygdala, which encode positive and negative valence of ethanol (EtOH)-related stimuli. Prior rodent studies have implicated these regions in regulation of punished EtOH self-administration (EtOH-SA).MethodsWe conducted in vivo electrophysiological recordings in mouse vmPFC and dmPFC to obtain neuronal correlates of footshock-punished EtOH-SA. Ex vivo recordings were performed in NAcS D1 receptor-expressing medium spiny neurons receiving vmPFC input to examine punishment-related plasticity in this pathway. Optogenetic photosilencing was employed to assess the functional contribution of the vmPFC, dmPFC, vmPFC projections to NAcS, or vmPFC projections to basolateral amygdala, to punished EtOH-SA.ResultsPunishment reduced EtOH lever pressing and elicited aborted presses (lever approach followed by rapid retraction). Neurons in the vmPFC and dmPFC exhibited phasic firing to EtOH lever presses and aborts, but only in the vmPFC was there a population-level shift in coding from lever presses to aborts with punishment. Closed-loop vmPFC, but not dmPFC, photosilencing on a postpunishment probe test negated the reduction in EtOH lever presses but not in aborts. Punishment was associated with altered plasticity at vmPFC inputs to D1 receptor-expressing medium spiny neurons in the NAcS. Photosilencing vmPFC projections to the NAcS, but not to the basolateral amygdala, partially reversed suppression of EtOH lever presses on probe testing.ConclusionsThese findings demonstrate a key role for the vmPFC in regulating EtOH-SA after punishment, with implications for understanding the neural basis of compulsive drinking in alcohol use disorder.

Dataset Information

Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer.

Publications

Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer.

Similar Datasets

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