Aluminum Maltolate-Induced Toxicity in NT2 Cells Occurs Through Apoptosis and Includes Cytochrome c Release

Aluminum (Al) compounds are neurotoxic and have been shown to induce experimental neurodegeneration although the mechanism of this effect is unclear. In order to study this neurotoxic effect of Al, we have developed an in vitro model system using Al maltolate and human NT2 cells. Al maltolate at 500 mM caused significant cell death with a 24-h incubation and this toxicity was even more evident after 48 h. Lower doses of Al maltolate were also effective, but required a longer incubation for cell death. Nuclear fragmentation suggestive of apoptosis was observed as early as three hours and increased substantially through 24 h. Chromatin condensation and nuclear fragmentation were confirmed by electron microscopy. In addition, TUNEL positive nuclei were also observed. The release of cytochrome c was demonstrated with Western blot analysis. This in vitro model using human cells adds to our understanding of Al neurotoxicity and could provide insight into the neurodegenerative processes in human disease

Peri-nuclear Clustering of Mitochondria is Triggered during Aluminum Maltolate Induced Apoptosis

Synapse loss and neuronal death are key features of Alzheimer’s disease pathology. Disrupted axonal transport of mitochondria is a potential mechanism that could contribute to both. As the major producer of ATP in the cell, transport of mitochondria to the synapse is required for synapse maintenance. However, mitochondria also play an important role in the regulation of apoptosis. Investigation of aluminum (Al) maltolate induced apoptosis in human NT2 cells led us to explore the relationship between apoptosis related changes and the disruption of mitochondrial transport. Similar to that observed with tau over expression, NT2 cells exhibit peri-nuclear clustering of mitochondria following treatment with Al maltolate. Neuritic processes largely lacked mitochondria, except in axonal swellings. Similar, but more rapid results were observed following staurosporine administration, indicating that the clustering effect was not specific to Al maltolate. Organelle clustering and transport disruption preceded apoptosis. Incubation with the caspase inhibitor zVAD-FMK effectively blocked apoptosis, however failed to prevent organelle clustering. Thus, transport disruption is associated with the initiation, but not necessarily the completion of apoptosis. These results, together with observed transport defects and apoptosis related changes in Alzheimer disease brain suggest that mitochondrial transport disruption may play a significant role in synapse loss and thus the pathogenesis or Alzheimer’s disease

Prevalence and predictors of poor mental health among pregnant women in Wales using a cross-sectional survey

Objectives To assess the prevalence of self-reported mental health problems in a cohort of women in early pregnancy. To describe the relationship between poor mental health and sociodemographic characteristics, self-efficacy and support networks. To assess if participants were representative of the local antenatal population. Research design and setting The UK government has pledged money to provide more support for women with perinatal mental health issues. Understanding the prevalence and predicting women who may need support will inform clinical practice. This paper reports part of the larger ‘Mothers Mood Study’, which explored women's and midwives’ experience of mild to moderate perinatal mental health issues and service provision. Routinely collected population level data were analysed and a smaller cross-sectional survey design used to assess predictors of poor mental health in early pregnancy in one health board in Wales. Participants Routinely collected data were extracted for all women who registered for maternity care between May 2017 and May 2018 (n = 6312) from the electronic maternity information system (pregnant population). Over a three month period 302 of these women completed a questionnaire at the antenatal clinic after an ultrasound scan (participants). Eligible women were aged ≥18 years, with sufficient spoken and written English to complete the questionnaire and a viable pregnancy of ≤18 weeks’ gestation. The questionnaire collected data on sociodemographic status, self-efficacy and support networks, self-reported mental health problems. Current anxiety and depression were assessed using the General Anxiety Disorders Assessment and Edinburgh Postnatal Depression Scale. Findings Among the pregnant population 23% (n = 1490) disclosed a mental health problem during routine questioning with anxiety and depression being the most common conditions. Participants completing the detailed questionnaire were similar in age and parity to the pregnant population with similar levels of depression (15.6%; n = 15.6 v 17.3%, n = 1092). Edinburgh Postnatal Depression Scale and General Anxiety Disorder 7 scores identified 8% with symptoms of anxiety (n = 25) or depression (n = 26) and a further 24.2% (n = 73) with symptoms of mild anxiety and 25.2% (n = 76) with mild depression. Low self-efficacy (OR 1.27, 95% CI 1.12–1.45), a previous mental health problem (OR 3.95, 95% CI 1.37–11.33) and low support from family (OR 1.13, 95% CI 1.00–1.27) were found to be associated with early pregnancy anxiety and/or depression. Key conclusions and implications for practice Around one in five women who register for maternity care may have a mental health problem. Mild to moderate anxiety and depression are common in early pregnancy. Services need to improve for women who do not currently meet the threshold for referral to perinatal mental health services. Assessment and active monitoring of mental health is recommended, in particular for pregnant women with risk factors including a history of previous mental health difficulties, poor family support or low self-efficacy

Choice of activity-intensity classification thresholds impacts upon accelerometer-assessed physical activity-health relationships in children

It is unknown whether using different published thresholds (PTs) for classifying physical activity (PA) impacts upon activity-health relationships. This study explored whether relationships between PA (sedentary [SED], light PA [LPA], moderate PA [MPA], moderate-to-vigorous PA, vigorous PA [VPA]) and health markers differed in children when classified using three different PTs

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Physical education contributes to total physical activity levels and predominantly in higher intensity physical activity categories

Children’s engagement in physical activity of a vigorous intensity or higher is more effective at promoting cardiorespiratory fitness than moderate physical activity. It remains unclear how higher intensity physical activity varies between days when schoolchildren participate in physical education (PE) and non-PE days. The purpose of this study was to assess how PE contributes to sedentary behaviour and the intensity profile of physical activity accumulated on PE days compared to non-PE days. Fifty-three schoolchildren (36 girls, 11.7 ± 0.3 years) completed five-day minute-by-minute habitual physical activity monitoring using triaxial accelerometers to determine time spent sedentary (<1.5 Metabolic Equivalent of Tasks (METs)) and in light (1.5–2.9 METs), moderate (3–5.9 METs), vigorous (6–8.9 METs), hard (9–11.9 METs) and very hard intensity (≥12 METs) physical activity on PE days and non-PE days. Sedentary time was higher on non-PE days than on PE days (mean difference: 62 minutes, p < 0.001). Hard and very hard intensity physical activity was significantly higher on PE days compared with non-PE days (mean total difference: 33 minutes, all significant at p < 0.001). During the PE lesson, boys spent more time in hard (p < 0.01) and very hard (p < 0.01) physical activity compared to girls. Schoolchildren spent significantly more time in higher intensity physical activity and significantly less time sedentary on PE days than on non-PE days. As well as reducing sedentary behaviour, the opportunity to promote such health-promoting higher intensity physical activity in the school setting warrants further investigation