Dietary Curdlan Enhances Bifidobacteria and Reduces Intestinal Inflammation in Mice

β-glucan consumption is known for its beneficial health effects, but the mode of action is unclear. While humans and mice lack the required enzymes to digest β-glucans, certain intestinal microbes can digest β-glucans, triggering gut microbial changes. Curdlan, a particulate β-glucan isolated from Alcaligenes faecalis, is used as a food additive. In this study we determined the effect of curdlan intake in mice on the intestinal microbiota and dextran sodium sulfate (DSS)-induced intestinal inflammation. The effect of curdlan on the human intestinal microbiota was assessed using i-screen, an assay for studying anaerobic microbial interactions. Mice received oral gavage with vehicle or curdlan for 14 days followed by DSS for 7 days. The curdlan-fed group showed reduced weight loss and colonic inflammation compared to the vehicle-fed group. Curdlan intake did not induce general microbiota community changes, although a specific Bifidobacterium, closely related to Bifidobacterium choerinum, was observed to be 10- to 100-fold more prevalent in the curdlan-fed group under control and colitis conditions, respectively. When tested in i-screen, curdlan induced a global change in the microbial composition of the healthy intestinal microbiota from a human. Overall, these results suggest that dietary curdlan induces microbiota changes that could reduce intestinal inflammation.     

Does crossing over repeated treatment with the dopamine reuptake inhibitors cocaine and BTCP modify their effects on cocaine-induced locomotion?

Because the dopamine reuptake inhibitors cocaine and BTCP produce different behavioral effects after repeated administration, we studied whether they could alter each other’s effects by examining the effects of crossing over repeated treatment with cocaine and BTCP on cocaine-induced locomotion. Male C57BL/6 mice were treated repeatedly with cocaine or BTCP during a first phase (days 1–3) and 3 days later, treated repeatedly with the same or the other compound during a second phase (days 7–9), after which they were administered one of several doses of cocaine on the next day. Locomotor activity was assessed after every daily treatment. The results show that 1) cocaine induced sensitization to its locomotor effects, 2) cocaine-induced sensitization was not altered by subsequent repeated treatment with BTCP, 3) initial repeated treatment with BTCP induced apparent cross-tolerance to cocaine, and 4) the initial effects of repeated BTCP were not markedly altered by subsequent repeated treatment with cocaine. The results indicate that the initial effects produced by repeated cocaine or BTCP are enduring and relatively difficult to alter by crossing over repeated treatment with the other compound. Thus, sensitization to the locomotor effects of cocaine in mice appeared to be attenuated by prior repeated treatment with BTCP but not reversed when followed by repeated treatment with BTCP. Received: 11 January 1998/Final version: 17 September 1998     

Behavioural specificity of chlordiazepoxide-produced StD

Low doses of benzodiazepines produce state-dependence (StD) of food-rewarded lever pressing in rats, and it has been hypothesized that the changes of memory states that can thus be studied constitute the mechanism whereby benzodiazepines cause their characteristic psychopharmacological actions such as anxiolysis, apparent memory loss and dependence. Non-benzodiazepine CNS agents such as NMDA antagonists also produce StD in this procedure, suggesting that the StD hypothesis of psychopharmacological drug action can be expanded to include agents other than benzodiazepines. For this expansion to be possible, however, it must be shown that the StD mechanism operates in a specific manner. The present experiments examined whether varying the extent of food deprivation affects any of a number of quantitative features of chlordiazepoxide (CDP)-induced StD of food-rewarded lever pressing in rats. The data indicate that the CDP doses required to generate StD in both drug-to-saline and dose-to-dose transfer tests, are considerably lower in relatively sated as opposed to more deprived animals; little or no difference was found in tests assaying saline-to-drug transfer. The data add behavioural to available pharmacological evidence supporting the hypothesis that changes of memory state constitute the mechanism whereby CNS agents such as benzodiazepines and NMDA antagonists cause their characteristic psychopharmacological actions. Some directions for future research are identified to explore further the pharmacological and behavioural specificity of drug-produced StD.     

Evaluation of an internet-based speech-in-noise screening test for school-age children

Objective: To evaluate a Dutch online speech-in-noise screening test (in Dutch: “Kinderhoortest”) in normal-hearing school-age children. Sub-aims were to study test–retest reliability, and the effects of presentation type and age on test results. Design: An observational cross-sectional study at school. Speech reception thresholds (SRTs) were obtained through the online test in a training condition, and two test conditions: on a desktop computer and smartphone. The order of the test conditions was counterbalanced. Study sample: Ninety-four children participated (5–12 years), of which 75 children were normal-hearing (≤25?dB HL at 0.5?kHz,?≤20?dB HL at 1–4?kHz). Results: There was a significant effect for test order for the two test conditions (first or second test), but not for presentation type (desktop computer or smartphone) (repeated measures analyses, F(1,75)?=?12.48, p?F(1,75)?=?0.01, p?=?0.982). SRT significantly improved by age year (first test: 0.25?dB SNR, 95% CI: –0.43 to –0.08, p?=?0.004. Second test: 0.29?dB SNR, 95% CI: –0.46 to –0.11; p?=?0.002). Conclusions: The online test shows potential for routine-hearing screening of school-age children, and can be presented on either a desktop computer or smartphone. The test should be evaluated further in order to establish sensitivity and specificity for hearing loss in children.     

Comparative studies of Toll-like receptor signalling using zebrafish

Zebrafish model systems for infectious disease are increasingly used for the functional analysis of molecular pattern recognition processes. These studies benefit from the high conservation level of all innate immune factors in vertebrates. Zebrafish studies are strategically well positioned for this because of the ease of comparisons with studies in other fish species of which the immune system also has been intensively studied, but that are currently still less amendable to detailed genetic or microscopic studies. In this paper we focus on Toll-like receptor (TLR) signalling factors, which currently are the best characterized in mammalian systems. We review the knowledge on TLR signalling in the context of recent advances in zebrafish studies and discuss possibilities for future approaches that can complement studies in cell cultures and rodent models. A focus in these comparisons is the role of negative control mechanisms in immune responses that appear very important in a whole organism to keep adverse systemic responses in check. We also pay much attention to comparisons with studies in common carp that is highly related to zebrafish and that because of its large body mass can complement immune studies in zebrafish.     

Sex-Specific Mechanism of Social Hierarchy in Mice

The establishment of social hierarchies is a naturally occurring, evolutionarily conserved phenomenon with a well-established impact on fitness and health. Investigations of complex social group dynamics may offer novel opportunities for translational studies of autism spectrum disorder. Here we describe a robust behavioral paradigm using an automated version of the tube test. Isogenic groups of male and female mice establish linear social hierarchies that remain highly stable for at least 14 days, the longest interval tested. Remarkably, however, their social strategy is sex-specific: females primarily utilize intrinsic attributes, whereas males are strongly influenced by prior social experience. Using both genetic and pharmacological manipulations, we identify testosterone as a critical sex-specific factor for determining which social strategy is used. Males inheriting a null mutation of the sex-determining region Y (Sry) gene used a similar social cognitive strategy as females. In contrast, females with transgenic expression of Sry utilized a typically male social strategy. Analogously, castration of males and testosterone supplementation of females yielded similar outcomes, with a reversal of their social cognitive strategy. Together, our results demonstrate a sex-specific mechanism underlying social hierarchy, in which both males and females retain the functional capacity to adapt their social strategy. More generally, we expect the automated tube test to provide an important complementary approach for both fundamental and translational studies of social behavior.