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  1. Article: Chronic alcohol intake regulates expression of SARS-CoV2 infection-relevant genes in an organ-specific manner.

    Friske, Marion M / Giannone, Francesco / Senger, Mona / Seitz, Robin / Hansson, Anita C / Spanagel, Rainer

    Alcohol (Hanover, York County, Pa.)

    2023  Volume 47, Issue 1, Page(s) 76–86

    Abstract: Background: Chronic alcohol consumption and alcohol use disorder have a tremendous impact on the patient's psychological and physiological health. There is evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but so far, the ... ...

    Abstract Background: Chronic alcohol consumption and alcohol use disorder have a tremendous impact on the patient's psychological and physiological health. There is evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but so far, the molecular mechanism underlying such an effect is unknown.
    Methods: We generated the expression data of SARS-CoV2 infection-relevant genes (Ace2, Tmprss2, and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. Ace2 and Tmprss2 represent the virus entry point, whereas Mas activates the anti-inflammatory response once the cells are infected.
    Results: Across three different chronic alcohol test conditions, we found a consistent upregulation of Ace2 gene expression in the lung, which has been shown to be the most affected organ in COVID-19 patients. Other organs such as liver, ileum, kidney, heart, and brain also showed upregulation of Ace2 and Mas gene expression but less consistently across the different animal models, while Tmprss2 expression was unaffected in all conditions.
    Conclusions: We conclude that alcohol-induced upregulation of Ace2 gene expression can lead to an elevated stochastic probability of virus entry into cells and may thus confer a molecular risk for SARS-CoV2 infection.
    MeSH term(s) Rats ; Animals ; COVID-19 ; Angiotensin-Converting Enzyme 2 ; RNA, Viral ; SARS-CoV-2 ; Alcohol Drinking
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; RNA, Viral
    Language English
    Publishing date 2023-02-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    DOI 10.1111/acer.14981
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Disrupted circadian expression of β-arrestin 2 affects reward-related µ-opioid receptor function in alcohol dependence.

    Meinhardt, Marcus W / Giannone, Francesco / Hirth, Nathalie / Bartsch, Dusan / Spampinato, Santi M / Kelsch, Wolfgang / Spanagel, Rainer / Sommer, Wolfgang H / Hansson, Anita C

    Journal of neurochemistry

    2022  Volume 160, Issue 4, Page(s) 454–468

    Abstract: There is increasing evidence for a daily rhythm of µ-opioid receptor (MOR) efficacy and the development of alcohol dependence. Previous studies show that β-arrestin 2 (bArr2) has an impact on alcohol intake, at least partially mediated via modulation of ... ...

    Abstract There is increasing evidence for a daily rhythm of µ-opioid receptor (MOR) efficacy and the development of alcohol dependence. Previous studies show that β-arrestin 2 (bArr2) has an impact on alcohol intake, at least partially mediated via modulation of MOR signaling, which in turn mediates the alcohol rewarding effects. Considering the interplay of circadian rhythms on MOR and alcohol dependence, we aimed to investigate bArr2 in alcohol dependence at different time points of the day/light cycle on the level of bArr2 mRNA (in situ hybridization), MOR availability (receptor autoradiography), and MOR signaling (Damgo-stimulated G-protein coupling) in the nucleus accumbens of alcohol-dependent and non-dependent Wistar rats. Using a microarray data set we found that bArr2, but not bArr1, shows a diurnal transcription pattern in the accumbens of naïve rats with higher expression levels during the active cycle. In 3-week abstinent rats, bArr2 is up-regulated in the accumbens at the beginning of the active cycle (ZT15), whereas no differences were found at the beginning of the inactive cycle (ZT3) compared with controls. This effect was accompanied by a specific down-regulation of MOR binding in the active cycle. Additionally, we detect a higher receptor coupling during the inactive cycle compared with the active cycle in alcohol-dependent animals. Together, we report daily rhythmicity for bArr2 expression linked to an inverse pattern of MOR, suggesting an involvement for bArr2 on circadian regulation of G-protein coupled receptors in alcohol dependence. The presented data may have implications for the development of novel bArr2-related treatment targets for alcoholism.
    MeSH term(s) Alcoholism/drug therapy ; Alcoholism/genetics ; Animals ; Circadian Rhythm/genetics ; Down-Regulation ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology ; Male ; Microarray Analysis ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Rats ; Rats, Wistar ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Opioid, mu/drug effects ; Receptors, Opioid, mu/genetics ; Reward ; beta-Arrestin 2/genetics
    Chemical Substances Arrb2 protein, rat ; Oprm1 protein, rat ; Receptors, G-Protein-Coupled ; Receptors, Opioid, mu ; beta-Arrestin 2 ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- (100929-53-1)
    Language English
    Publishing date 2022-01-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.15559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Chronic alcohol intake regulates expression of SARS-CoV2 infection-relevant genes in an organ-specific manner

    Friske, Marion M / Giannone, Francesco / Senger, Mona / Seitz, Robin / Hansson, Anita C / Spanagel, Rainer

    bioRxiv

    Abstract: Chronic alcohol consumption and alcohol use disorder (AUD) have a tremendous impact on the patients psychological and physiological health. There is some evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but the molecular ... ...

    Abstract Chronic alcohol consumption and alcohol use disorder (AUD) have a tremendous impact on the patients psychological and physiological health. There is some evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but the molecular mechanism is unknown. Here, we generated expression data of SARS-CoV2 infection relevant genes (Ace2, Tmprss2 and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. ACE2 and TMPRSS2 represent the virus entry point whereas Mas is activating the anti-inflammatory response once the cells are infected. Across three different chronic alcohol test conditions, we found a consistent up-regulation of Ace2 in the lung, which is the most affected organ in Covid-19 patients. Other organs such as liver, ileum, kidney, heart, and the brain showed also up-regulation of Ace2 and Mas but in a less consistent manner across the different animal models, while Tmprss2 was unaffected in all conditions. We suggest that alcohol-induced upregulation of Ace2 can lead to an elevated stochastic probability of cellular virus entry and may thus confer a molecular risk factor for a SARS-CoV2 infection.
    Keywords covid19
    Language English
    Publishing date 2022-02-02
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.02.01.478685
    Database COVID19

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