Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression
| Autor: | Kolter Grigsby, Courtney Ledford, Tanvi Batish, Snigdha Kanadibhotla, Delaney Smith, Evan Firsick, Alexander Tran, Kayla Townsley, Kaylee-Abril Vasquez Reyes, Katherine LeBlanc, Angela Ozburn |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
circadian
alcohol nucleus accumbens suprachiasmatic nucleus ventral tegmental area gene expression Ethanol Phosphoric Diester Hydrolases Organic Chemistry Gene Expression General Medicine Catalysis Computer Science Applications Binge Drinking Circadian Rhythm Thalidomide Inorganic Chemistry Mice Inbred C57BL Mice Animals Physical and Theoretical Chemistry Molecular Biology Casein Kinases Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11084 |
| ISSN: | 1422-0067 |
| Popis: | Previous studies (1) support a role of circadian genes in regulating alcohol intake, and (2) reveal that harmful alcohol use alters circadian rhythms. However, there is minimal knowledge of the effects of chronic alcohol processes on rhythmic circadian gene expression across brain regions important for circadian biology and alcohol intake. Therefore, the present study sought to test the effects of chronic binge-like drinking on diurnal circadian gene expression patterns in the master circadian pacemaker (SCN), the ventral tegmental area (VTA), and the nucleus accumbens (NAc) in High Drinking in the Dark-1 (HDID-1) mice, a unique genetic risk model for drinking to intoxication. Consistent with earlier findings, we found that 8 weeks of binge-like drinking reduced the amplitude of several core circadian clock genes in the NAc and SCN, but not the VTA. To better inform the use of circadian-relevant pharmacotherapies in reducing harmful drinking and ameliorating alcohol’s effects on circadian gene expression, we tested whether the casein kinase-1 inhibitor, PF-67046, or the phosphodiesterase type-4 (an upstream regulator of circadian signalling) inhibitor, apremilast, would reduce binge-like intake and mitigate circadian gene suppression. PF-67046 did not reduce intake but did have circadian gene effects. In contrast, apremilast reduced drinking, but had no effect on circadian expression patterns. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|