Effects of low dose of ethanol on the senescence score, brain function and gene expression in senescence-accelerated mice 8 (SAMP8)

Abstract

Accumulating epidemiological evidence suggests light to moderate alcohol intake reduces risk of several chronic diseases. However, there is limited information regarding the effects of low alcohol intake in animal studies. This study investigated the effect of low ethanol dosage on senescence-accelerated mouse (SAMP8), an animal model of aging and neurodegenaration. Male SAMP8 mice (11 weeks old) had free access to a commercial stock diet with drinking water containing 0, 1 or 2% (v/v) ethanol for 15 weeks. The total grading score of senescence in the 1%-ethanol group was, in large part, the lowest among the three groups. Analysis using the open-field test revealed a significant elevation (+77%, P<0.05) in the rearing activity (index of seeking behavior) in the 1%-ethanol group, but not in the 2%-ethanol group. In addition, 2% ethanol elevated spontaneous locomotor activity (+75%, P<0.05), whereas 1% ethanol did not. Scrutiny of serum parameters indicated intake of 1% ethanol significantly decreased serum insulin levels (−13%, P<0.05), whereas 2% did not. Intake of 2% ethanol significantly elevated (2.5-fold, P<0.05) S100a8 mRNA (an inflammatory signal) in the brain, but that of 1% ethanol did not. Intriguingly, 1% ethanol intake remarkably elevated (10-fold, P<0.05) mRNA of brain alcohol dehydrogenase 1 (Adh1), which metabolizes lipid-peroxidation products and is involved in the synthesis of retinoic acid, a neuroprotective factor. Of note, 2%-ethanol intake did not exert this effect. Taken together, intake of 1% ethanol is likely to be beneficial for SAMP8 mice.

Low-Dose Ethanol Has Impacts on Plasma Levels of Metabolites Relating to Chronic Disease Risk in SAMP8 mice

“…Consistent with findings from our previous study (8), the total senescence grading score in the 1% ethanol group was the lowest among the four treatment groups, whereas the scores of the 2% and 5% ethanol groups did not differ from those of the control. Furthermore, the present study revealed that, when compared against the control group, only mice given 1% ethanol had greater limb grip strength at 21 wk.…”

“…This data suggests that 1% ethanol may be favorable for senescence and muscle strength, but not 2% and 5% ethanol, thereby supporting the J-curve hypothesis of alcohol. Of note, we previously reported that 2% ethanol stimulated spontaneous locomotor movement in SAMP8 mice, but 1% ethanol did not (8); thus, the enhanced limb grip strength observed in mice given 1% ethanol is likely to be unrelated.…”

“…Collectively, the results imply that low-dose ethanol may have beneficial effect on aging mice by elevating hippurate. Recent studies suggest that low-dose ethanol inhibits oxidative stress via the upregulation of anti-oxidant systems such as cystathionine g-lyase and alcohol dehydrogenase 1 (8,10). Since low-dose ethanol elevated hippurate levels in our mice, it is presumable this would have a beneficial impact on the aforementioned conditions, warranting mechanistic studies.…”

Consumption of Low-Dose of Ethanol Suppresses Colon Tumorigenesis in 1,2-Dimethylhydrazine-Treated Rats

“…To the best of our knowledge, this study is the first to reveal that consumption of 0.5-1% ethanol suppresses colon tumorigenesis in DMH-treated rats, but that of 2% ethanol does not. The results are similar to those of our previous studies indicating that 1% ethanol exerted a beneficial effect on the liver function in rats fed a highfat diet (14) and on the aging process in SAMP8 mice, whereas 2% ethanol exhibited lesser effects (15). Collectively, consumption of 1% ethanol may offer health benefits, whereas that of 2% ethanol may offer lesser benefits, supporting the J-curve hypothesis for the effect of alcohol on health.…”

“…Recently, we reported that consumption of 1% (v/v) ethanol in drinking water improved the liver function in rats fed a high-fat diet (13) and delayed the aging process in senescence-accelerated mice (SAMP8), whereas 2% (v/v) ethanol exhibited a minimal effect on the liver function and aging (14). These studies exhibit a clear beneficial effect of 1% ethanol but less so for 2% ethanol, supporting the J-curve hypothesis of alcohol consumption.…”