Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism, and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine beta-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism.
Purpose Research has demonstrated cognitive benefits following acute polyphenol-rich berry consumption in children and young adults. Berry intake also has been associated with metabolic benefits. No study has yet examined cognitive performance in middle-aged adults. We investigated the relationships among cognitive and metabolic outcomes in middle-aged adults following wild blueberry (WBB) consumption. Methods Thirty-five individuals aged 40–65 years participated in a randomized, double blind, cross-over study. Participants consumed a breakfast meal and 1-cup equivalent WBB drink or matched placebo beverage on two occasions. Participants completed cognitive tasks and had blood drawn before and at regular intervals for 8 h after each meal/treatment. Changes in episodic memory and executive function (EF) were assessed alongside plasma levels of glucose, insulin, and triglyceride. Results Analysis of the memory-related Auditory Verbal Learning Task (AVLT) word recognition measure revealed a decrease in performance over the test day after placebo intake, whereas performance after WBB was maintained. For the AVLT word rejection measure, participants identified more foils following WBB in comparison to placebo. Benefits were also observed for EF on the Go/No-Go task with fewer errors following WBB intake on cognitively demanding invalid No-Go trials in comparison to placebo. Furthermore, in comparison to placebo, response times were faster for the Go/No-Go task, specifically at 4 h and 8 h following WBB treatment. We also observed reduced post-meal glucose and insulin, but not triglyceride, concentrations in comparison to placebo over the first 2 h following ingestion. Though the addition of Age, BMI, glucose and insulin as covariates to the analysis reduced the significant effect of beverage for AVLT word rejection, metabolic outcomes did not interact with treatment to predict cognitive performance with the exception of one isolated trend. Conclusions This study indicated acute cognitive benefits of WBB intake in cognitively healthy middle-aged individuals, particularly in the context of demanding tasks and cognitive fatigue. WBB improved glucose and insulin responses to a meal. Further research is required to elucidate the underlying mechanism by which WBB improves cognitive function.
BACKGROUND: Fibers’ properties impact different mechanisms involved in satiety and energy intake regulation and metabolic outcomes.OBJECTIVE: Evaluate the effect of fiber types and menopausal status on satiety and metabolic responses in overweight women.METHODS: In a randomized within-subjects design, 19 overweight/obese women [9 premenopausal and 10 postmenopausal] consumed 3 preloads that varied by fiber content and source: 1) 3:1 ratio of soluble:insoluble fiber (SF), 2) 1:3 ratio of soluble:insoluble fiber (IF), 3) no fiber control (NFC). Subjective satiety, cholecystokinin (CCK), glucose, insulin, and triglyceride (TG) were measured for 3 h post-preload followed by in-lab ad libitum test meal and 32 hour food intake monitoring.RESULTS: Significant preload, time and preload by menopausal status interaction was apparent for hunger and fullness (p < 0.05 for both) with SF preload predominantly more satiating in postmenopausal women. CCK and insulin were significantly lower after SF preload (p < 0.0001 for both). Post-preload glucose responses differed by menopausal status: postmenopausal women distinguished between fiber types unlike premenopausal women (p = 0.02). TG was significantly elevated after the IF preload compared to NFC and SF (p = 0.007 and p = 0.008, respectively).CONCLUSIONS: Customized/personalized dietary recommendations for women during their premenopausal and postmenopausal years can help maximize metabolic and appetite control.
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