Exposure to environmental enrichment elicits differential hippocampal cell proliferation: role of individual responsiveness to anxiety

Environmental enrichment (EE) is a largely employed behavioral procedure in which animals are exposed to high stimulation compared with conventional housing conditions. Animal exposure to an EE exerts beneficial effects on the performance of different learning tasks and induces a number of behavioral, neurochemical, and neuroanatomical changes including hippocampal cell proliferation. However, the importance of voluntary interaction with the environment in these changes has not been clearly resolved yet. Moreover, the effects of a complex environment on animal emotionality still remains questionable and has not been explored in detail under conditions that allow unmasking individual responses among subjects in a group. The present study was aimed at exposing groups of rats to an EE, and analyzing individual differences in activity levels during EE sessions. We observed differences with respect to the activity level displayed by rats during the enriched sessions, which correlated with differences in the rate of hippocampal cell proliferation. It is suggested that exposure to EE may reduce anxiety-like behaviors and may elicit individual differences on emotional reactions positively linked with hippocampal neurogenesis and testosterone levels.     

Bullying and Victimization in Overweight and Obese Outpatient Children and Adolescents: An Italian Multicentric Study

Objective

Being overweight or obese is one of the most common reasons that children and adolescents are teased at school. We carried out a study in order to investigate: i) the relation between weight status and school bullying and ii) the relation between weight status categories and types of victimization and bullying in an outpatient sample of Italian children and adolescents with different degrees of overweight from minimal overweight up to severe obesity.

Participants/Methods

Nine-hundred-forty-seven outpatient children and adolescents (age range 6.0–14.0 years) were recruited in 14 hospitals distributed over the country of Italy. The participants were classified as normal-weight (N = 129), overweight (N = 126), moderately obese (N = 568), and severely obese (N = 124). The nature and extent of verbal, physical and relational bullying and victimization were assessed with an adapted version of the revised Olweus bully-victim questionnaire. Each participant was coded as bully, victim, bully-victim, or not involved.

Results

Normal-weight and overweight participants were less involved in bullying than obese participants; severely obese males were more involved in the double role of bully and victim. Severely obese children and adolescents suffered not only from verbal victimization but also from physical victimization and exclusion from group activities. Weight status categories were not directly related to bullying behaviour; however severely obese males perpetrated more bullying behaviour compared to severely obese females.

Conclusions

Obesity and bullying among children and adolescents are of ongoing concern worldwide and may be closely related. Common strategies of intervention are needed to cope with these two social health challenges.     

3D Imaging Detection of HER2 Based in the Use of Novel Affibody-Quantum Dots Probes and Ratiometric Analysis

Patients with breast cancer (BC) overexpressing HER2 (HER2+) are selected for Trastuzumab treatment, which blocks HER2 and improves cancer prognosis. However, HER2+ diagnosis, by the gold standard, immunohistochemistry, could lead to errors, associated to: a) variability in sample manipulation (thin 2D sections), b) use of subjective algorithms, and c) heterogeneity of HER2 expression within the tissue. Therefore, we explored HER2 3D detection by multiplexed imaging of Affibody-Quantum Dots conjugates (Aff-QD), ratiometric analysis (RMA_FI) and thresholding, using BC multicellular tumor spheroids (BC-MTS) (~120 μm of diameter) as 3D model of BC. HER2+, HER2– and hybrid HER2+/? BC-MTS (mimicking heterogeneous tissue) were incubated simultaneously with two Aff-QD probes (anti-HER2 and negative control (NC), respectively, (1:1)). Confocal XY sections were recorded along the Z distance, and processed by automatized RMA_FI (anti-HER2 Aff-QD/ NC). Quantifying the NC fluorescence allowed to predict the fraction of non-specific accumulation of the anti-HER2 probe within the thick sample, and resolve the specific HER2 level. HER2 was detected up to 30 μm within intact BC-MTS, however, permeabilization improved detection up to 70 μm. Specific HER2 signal was objectively quantified, and HER2 3D-density of 9.2, 48.3 and 30.8% were obtained in HER2?, HER2+ and hybrid HER2+/? permeabilized BC-MTS, respectively. Therefore, by combining the multiplexing capacity of Aff-QD probes and RMA_FI, we overcame the challenge of non-specific probe accumulation in 3D samples with minimal processing, yielding a fast, specific spatial HER2 detection and objective quantification.     

Sex hormones regulate metainflammation in diet-induced obesity in mice

Men have a statistically higher risk of metabolic and cardiovascular disease than premenopausal women, but the mechanisms mediating these differences are elusive. Chronic inflammation during obesity contributes to disease risk and is significantly more robust in males. Prior work demonstrated that compared with obese males, obese females have reduced proinflammatory adipose tissue macrophages (ATMs). Given the paucity of data on how sex hormones contribute to macrophage responses in obesity, we sought to understand the role of sex hormones in promoting obesity-induced myeloid inflammation. We used gonadectomy, estrogen receptor–deficient alpha chimeras, and androgen-insensitive mice to model sex hormone deficiency. These models were evaluated in diet-induced obesity conditions (high-fat diet [HFD]) and in vitro myeloid assays. We found that ovariectomy increased weight gain and adiposity. Ovariectomized females had increased ATMs and bone marrow myeloid colonies compared with sham-gonadectomized females. In addition, castrated males exposed to HFD had improved glucose tolerance, insulin sensitivity, and adiposity with fewer Ly6c^hi monocytes and bone marrow myeloid colonies compared with sham-gonadectomized males, although local adipose inflammation was enhanced. Similar findings were observed in androgen-insensitive mice; however, these mice had fewer CD11c⁺ ATMs, implying a developmental role for androgens in myelopoiesis and adipose inflammation. We concluded that gonadectomy results in convergence of metabolic and inflammatory responses to HFD between the sexes, and that myeloid estrogen receptor alpha contributes minimally to diet-induced inflammatory responses, whereas loss of androgen-receptor signaling improves metabolic and inflammatory outcomes. These studies demonstrate that sex hormones play a critical role in sex differences in obesity, metabolic dysfunction, and myeloid inflammation.     

Correction to: Chronic Administration of S-Allylcysteine Activates Nrf2 Factor and Enhances the Activity of Antioxidant Enzymes in the Striatum,Frontal Cortex and Hippocampus

Neurochemical Research - The original version of this article unfortunately contained a mistake.     

In silico scaffold evaluation and solid phase approach to identify new gelatinase inhibitors

Among matrix metalloproteinases (MMPs), gelatinases MMP-2 (gelatinase A) and MMP-9 (gelatinase B) play a key role in a number of physiological processes such as tissue repair and fibrosis. Many evidences point out their involvement in a series of pathological events, such as arthritis, multiple sclerosis, cardiovascular diseases, inflammatory processes and tumor progression by degradation of the extracellular matrix. To date, the identification of non-specific MMP inhibitors has made difficult the selective targeting of gelatinases. In this work we report the identification, design and synthesis of new gelatinase inhibitors with appropriate drug-like properties and good profile in terms of affinity and selectivity. By a detailed in silico protocol and innovative and versatile solid phase approaches, a series of 4-thiazolydinyl-N-hydroxycarboxyamide derivatives were identified. In particular, compounds 9a and 10a showed a potent inhibitory activity against gelatinase B and good selectivity over the other MMP considered in this study. The identified compounds could represent novel potential candidates as therapeutic agents.     

Medical Students’ Attitudes towards Overweight and Obesity

Objective

Studies from the USA have identified medical students as a major source of stigmatizing attitudes towards overweight and obese individuals. As data from Europe is scarce, medical students’ attitudes were investigated at the University of Leipzig in Leipzig, Germany.

Design

Cross-sectional survey containing an experimental manipulation consisting of a pair of vignettes depicting an obese and a normal weight 42-year-old woman, respectively. Vignettes were followed by the Fat Phobia Scale (FPS), a semantic differential assessing weight related attitudes. In case of the overweight vignette a panel of questions on causal attribution for the overweight preceded administration of the FPS.

Subjects

671 medical students were enrolled at the University of Leipzig from May to June 2011.

Results

The overweight vignette was rated significantly more negative than the normal weight vignette (mean FPS score 3.65±0.45 versus 2.54±0.38, p<0.001). A higher proportion of students had negative attitudes towards the overweight as compared to the normal weight individual (98.9% versus 53.7%, p<0.001). A “positive energy balance” was perceived as the most relevant cause for the overweight, followed by “negligent personality trait”, “societal and social environment” and “biomedical causes”. Attributing a “positive energy balance” or “negligent personality trait” as relevant cause for the overweight was positively associated with negative attitudes.

Conclusion

The results of this study confirm and complement findings from other countries, mainly the USA, and indicate that weight bias in the health care setting may be a global issue. Stigmatizing attitudes towards overweight and obesity are prevalent among a sample of medical students at the University of Leipzig. Negative attitudes arise on the basis of holding the individual accountable for the excess weight. They call for bringing the topic of overweight and obesity more into the focus of the medical curriculum and for enhancing medical students’ awareness of the complex aetiology of this health condition.     

Steroidal 5α-reductase inhibitors using 4-androstenedione as substrate

The aim of this study was to determine the capacity of some progesterone derivatives, to inhibit the conversion of labeled androstenedione ([(3)H] 4-dione) to [(3)H]dihydrotestosterone ([(3)H]DHT) in prostate nuclear membrane fractions, where the 5α-reductase activity is present. The enzyme 5α-reductase catalyzes the 5α-reduction of 4-dione whereas the 17β-hydroxysteroid dehydrogenase catalyzes the transformation of 4-dione to testosterone or 5α-dione to dihydrotestosterone (DHT). Moreover, we also investigated the role of unlabeled 5α-dione in these pathways. In order to determine the inhibitory effect of different concentrations of the progesterone derivatives in the conversion of [(3)H] 4-dione to [(3)H]DHT, homogenates of human prostate were incubated with [(3)H] 4-dione, NADPH and increasing concentrations of non-labeled 5α-dione. The incubating mixture was extracted and purified using thin layer chromatography. The fraction of the chromatogram corresponding to the standard of DHT was separated and the radioactivity determined. The results showed that the presence of [(3)H] 4-dione plus unlabelled 5α-dione produced similar levels of DHT as compared to [(3)H] 4-dione. On the other hand, the results indicated that 17α-hydroxypregn-4-ene-3,20-dione 5 and 4-bromo-17α-hydroxypregn-4-ene-3,20-dione 7b, were the most potent steroids to inhibit the conversion of [(3)H] 4-dione to [(3)H]DHT, showing IC(50) values of 2 and 1.6?nM, respectively.     

Effectiveness of a Video-Feedback and Questioning Programme to Develop Cognitive Expertise in Sport

The importance within sport expertise of cognitive factors has been emphasised in many research studies. Adaptations that take place in athletes’ long-term memories are going to condition their decision-making and performance, and training programmes must be developed that improve these adaptations. In our study, we provide a tactical-cognitive training programme based on video-feedback and questioning in order to improve tactical knowledge in tennis players and verify its effect when transferred to athletes’ decision-making. 11 intermediate tennis players participated in this study (12.9±0.7 years old), distributed into two groups (experimental, n = 5; control, n = 6). Tactical knowledge was measured by problem representation and strategy planning with a verbal protocol. Decision-making was measured by a systematic observation instrument. Results confirm the effectiveness of a combination of video-feedback and questioning on cognitive expertise, developing adaptations in long-term memory that produce an improvement in the quality of tactical knowledge (content, sophistication and structure). This, in turn, is transferred to the athletes’ decision-making capacity, leading to a higher percentage of successful decisions made during game play. Finally, we emphasise the need to develop effective programmes to develop cognitive expertise and improve athletes'' performance, and include it in athletes’ formative stages.