Anxiety in Mice: A Principal Component Analysis Study

Two principal component analyses of anxiety were undertaken investigating two strains of mice (ABP/Le and C57BL/6ByJ) in two different experiments, both classical tests for assessing anxiety in rodents. The elevated plus-maze and staircase were used for the first experiment, and a free exploratory paradigm and light-dark discrimination were used for the second. The components in the analyses produced definitions of four fundamental behavior patterns: novelty-induced anxiety, general activity, exploratory behavior, and decision making. We also noted that the anxious phenotype was determined by both strain and experimental procedure. The relationship between behavior patterns and the use of specific tests plus links with the genetic background are discussed

Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation

Gene transcription is required for long-term memory (LTM) formation. LTM formation is impaired in a male-specific manner in mice lacking either of the two Ca2+/calmodulin-dependent kinase kinase (Camkk) genes. Since altered transcription was suggested to cause these impairments in LTM formation, we used microarrays to screen for CaMKKβ-dependent gene expression changes. Here we show that the hippocampal mRNA expression of two splicing factors, splicing factor arginine/serine-rich 3 (Sfrs3/Srp20) and polypyrimidine tract-binding protein-associated splicing factor (Psf), is altered in CaMKKβ-deficient males. In wild-type (WT) mice, the basal expression level in the hippocampus is higher in males than in females, and the sex difference in Srp20 expression is detectable before puberty. Training in two hippocampus-dependent learning tasks, the spatial version of the Morris water maze (MWM) and background contextual fear conditioning, increases the hippocampal mRNA expression of both splicing factors in WT males. However, the increase in Srp20 mRNA expression occurs only in males and not in females, whereas the up-regulation of Psf expression occurs in both sexes. Importantly, control experiments demonstrate that the up-regulation of both splicing factors is specific for the learned associations after contextual fear conditioning. In summary, we provide the first evidence for a regulation of splicing factors during LTM formation and we suggest that alternative splicing contributes to sex differences in LTM formation

Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study

The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. Methods. Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045–45 y/o, smokers, and small drinkers (24-hour urinary volume <1 L and osmolality >700 mOsmol/kg). Outcomes. 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. Test Group. Subjects consumed 1.5 L daily of the study product (EVIAN) on top of their usual water intake for 50 days. Control Group. Subjects continued their usual lifestyle habits. Results. 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary

Consumption of a Carbonated Beverage with High-Intensity Sweeteners Has No Effect on Insulin Sensitivity and Secretion in Nondiabetic Adults

International audienceBackground The effects of the regular intake of beverages containing high-intensity sweeteners on insulin sensitivity in healthy individuals remain controversial. Objective This trial compared the effects of the consumption of a carbonated beverage containing aspartame and acesulfame K (high-intensity sweeteners beverage-HISB) with those of an unsweetened, no-calorie carbonated beverage (UB) on insulin sensitivity and secretion in nondiabetic adults. Methods SEDULC was a randomized, double-blind, crossover study. Nondiabetic adults [mean age 31 y, 44% men, body mass index (BMI; kg/m(2)) 19-29] who did not consume high-intensity sweeteners were randomized 1 1 to drink 1 of the 2 carbonated beverages, 2 cans (330 mL each)/d, for 12 wk. After a 4-wk washout period, participants were switched to the opposite beverage for 12 wk. The primary outcome tested was the change in insulin sensitivity as assessed by the Matsuda Insulin Sensitivity Index (MISI) after an oral glucose load. Secondary outcomes were indexes of insulin secretion. Results Sixty individuals were enrolled and 50 completed the study (28 nonoverweight and 22 overweight participants). The change in MISI from baseline did not significantly differ between beverages and noninferiority was demonstrated (difference = -0.23; 95% CI -1.31, 0.85; P < 0.0001). The change in insulinogenic (means +/- SEMs 0.23 +/- 0.14 for HISB compared with 0.08 +/- 0.1 for UB) and disposition indexes (2.70 +/- 0.99 for HISB compared with 1.62 +/- 0.90 for UB) did not differ, and no differences in insulin secretion estimates were confirmed by the Stumvoll indexes. Consuming the high-intensity sweeteners did not affect body weight, self-reported dietary consumption, or self-reported physical activity. Conclusions These findings suggest that the daily consumption of 2 cans of a beverage containing aspartame and acesulfame K over 12 wk has no significant effect on insulin sensitivity and secretion in nondiabetic adults. This trial was registered at clinicaltrials.gov as NCT02031497