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This report aims to provide a better understanding of physical activity (PA) and related factors among Spanish children and adolescents living with disabilities. The 10 indicators used for the Global Matrix on Para Report Cards of children and adolescents living with disabilities were evaluated based on the best available data in Spain. An analysis of strengths, weaknesses, opportunities, and threats based on data provision was drafted by three experts and critically reviewed by the authorship team to provide a national perspective for each evaluated indicator. Government was the indicator with the highest grade (C+), followed by Sedentary Behaviors (C-), School (D), Overall PA (D-), and Community & Environment (F). The remaining indicators received an incomplete grade. There were low levels of PA in Spanish children and adolescents living with disabilities. Yet, opportunities to improve the current surveillance of PA among this population exist.

The aim of this study was to study different ‘healthy profiles’ through the impact of multiple lifestyle behaviours (sleep patterns, screen time and quality diet) on active commuting to school (ACS) in adolescents. Sixteen secondary schools from four Spanish cities were randomly selected. All participants filled in an “Ad-Hoc” questionnaire to measure their mode of commuting and distance from home to school and their lifestyle behaviours. A multivariate logistic regression model was performed to analyse the main predictor variables of ACS. The final sample was 301 adolescents (50.2% girls; mean age ± SD: 14.9 ± 0.48 years). The percentage of ACS was 64.5%. Multiple logistic regressions showed: boys were more active commuters than girls [OR = 2.28 (CI 95%: 1.12−4.64); p = 0.02]; adolescents who lived farther had lower probability to ACS [OR = 0.74 (CI 95%: 0.69−0.80); p < 0.001]; adolescents who met sleep duration recommendations were more likely to ACS [OR = 3.05 (CI 95%: 1.07−8.69); p = 0.04], while with each hour of sleep, the odds of ACS was reduced [OR = 0.51 (CI 95%: 0.30−0.89); p = 0.02]; higher odds were shown to ACS in adolescents who have more adherence to MD [OR = 1.16(CI 95%: 1.00−1.33); p = 0.05]; and habitual breakfast consumption was inversely associated with ACS [OR = 0.41 (CI: 95%: 0.18−0.96); p = 0.04]. ACS was associated with being a boy, living at a shorter distance to school, a daily sleep time ≥ 8 h and presented a higher adherence to MD.

Background: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children's and adolescents' (5-17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions., Methods: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders' top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country., Results: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally., Conclusions: The Global Matrix 4.0 represents the largest compilation of children's and adolescents' PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.

Active commuting to school (ACS) seems to be one of the means to increase physical activity (PA) levels in youth, but it is unclear if ACS reduces the prevalence of obesity, protecting and improving their health. Most of the previous research has been conducted on children or youth (i.e., children with adolescents together), and there is a paucity of research in adolescents only. The purpose of this review was to assess the association between ACS with overweight/obesity parameters in adolescents aged 11 to 19 years. We used PubMed, WOS and SPORTDiscus as electronics databases. All steps of the process followed the recommendations of the PRISMA flow-diagram. Fifteen articles (68.18%) found a consistent association between ACS and body composition and seven studies (31.82%) showed no differences in body composition between active and passive commuters to school. Fourteen studies observed that active commuters to school had a more favorable body composition and one study reported that ACS was associated with unfavourable body composition. ACS could be the steppingstone to improve PA promotion in adolescence but whether ACS is associated with improved body composition and prevention of obesity requires further research.

Background: Multiple system atrophy (MSA) is a rare, progressive, neurodegenerative disorder presenting glia pathology. Still, disease etiology and pathophysiology are unknown, but neuro-inflammation and vascular disruption may be contributing factors to the disease progression. Here, we performed an ex vivo deep proteome profiling of the prefrontal cortex of MSA patients to reveal disease-relevant molecular neuropathological processes. Observations were validated in plasma and cerebrospinal fluid (CSF) of novel cross-sectional patient cohorts., Methods: Brains from 45 MSA patients and 30 normal controls (CTRLs) were included. Brain samples were homogenized and trypsinized for peptide formation and analyzed by high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results were supplemented by western blotting, immuno-capture, tissue clearing and 3D imaging, immunohistochemistry and immunofluorescence. Subsequent measurements of glial fibrillary acid protein (GFAP) and neuro-filament light chain (NFL) levels were performed by immunoblotting in plasma of 20 MSA patients and 20 CTRLs. Finally, we performed a proteome profiling of 144 CSF samples from MSA and CTRLs, as well as other parkinsonian disorders. Data were analyzed using relevant parametric and non-parametric two-sample tests or linear regression tests followed by post hoc tests corrected for multiple testing. Additionally, high-throughput bioinformatic analyses were applied., Results: We quantified more than 4,000 proteins across samples and identified 49 differentially expressed proteins with significantly different abundances in MSA patients compared with CTRLs. Pathway analyses showed enrichment of processes related to fibrinolysis and complement cascade activation. Increased fibrinogen subunit β (FGB) protein levels were further verified, and we identified an enriched recognition of FGB by IgGs as well as intra-parenchymal accumulation around blood vessels. We corroborated blood-brain barrier leakage by a significant increase in GFAP and NFL plasma levels in MSA patients that correlated to disease severity and/or duration. Proteome profiling of CSF samples acquired during the disease course, confirmed increased total fibrinogen levels and immune-related components in the soluble fraction of MSA patients. This was also true for the other atypical parkinsonian disorders, dementia with Lewy bodies and progressive supra-nuclear palsy, but not for Parkinson's disease patients., Conclusion: Our results implicate activation of the fibrinolytic cascade and immune system in the brain as contributing factors in MSA associated with a more severe disease course., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Increased physical activity (PA) is a very important factor in a healthy aging lifestyle. Psychosocial factors have also a main role in the initiation and maintenance of this behavior, but nowadays its implications for frailty elderly people are unknown, therefore, the aim of this study was to identify the psychosociological variables of behavior change that influence the practice of (PA) in frail and prefrail elderly., Methods: A total of 103 frail and pre-frail elderly people (72 females) participated in this cross-sectional study, on the framework of the EXERNET-Elder3.0 project. Age ranged from 68-94 years (mean = 80.4 ± 5.9 years). Individualized face-to-face interviews according to the constructs of the Transtheoretical Model of Change (TTM) [(decisional balance (DB) and self-efficacy (SE)], social support (SS) (family and friends) and outcome expectations (OE) were administered to all participants., Results: Significant differences were found in DB, perceived benefits (PBn), SE, family-related SS and OE as a function of stages of change (SoC) (p < 0.005), but no significant were found in perceived barriers (PBrr) (p = 0.259) and friends-related SS (p = 0.068). According to the Scheffé post-hoc test, those in advanced SoC (Action-Maintenance), scored higher than those in lower SoC (Precontemplation-Contemplation and Preparation)., Conclusion: The scores obtained from the study variables differed according to the SoC, supporting the external validity for the use of the TTM in frailty elderly. Further research is needed to determine the impact of PBrr and friends-related SS on this people, as well as to identify the validity of this model in the long-term in this population., (© 2022. The Author(s).)

The aims of this study were to determine for the first time the prevalence of a national sample of Spanish minors meeting the 24-h movement guidelines; to determine their correlates; and to examine their associations with socioemotional behavioral problems. Cross-sectional data from the Spanish National Health Survey (2017) were analyzed for this study. A total of 3772 Spanish minors were included. Physical activity was parent-reported by a modified short version of the International Physical Activity Questionnaire, which included a single question related to the participation in physical activity in free time. Recreational screen time was parent-reported by asking respondents for weekdays and weekends independently: "How much time does your child typically spend in front of a screen, including a computer, tablet, television, video, video game, or cell phone screen?". Sleep duration was parent-reported by the following question: "Can you tell me approximately how many hours your child usually sleeps daily?". The Strengths and Difficulties Questionnaire was applied for the evaluation of socioemotional behavioral problems. The prevalence of meeting of all the three guidelines was 13.5%. Compared to meeting all guidelines, higher odds of socioemotional behavioral problems were found in participants meeting two guidelines (OR = 1.42; CI95%, 1.10-1.83), one guideline (OR = 1.50; 95%CI,1.14-1.96), or none of the guidelines (OR = 1.92; 95%CI,1.30-2.83). Our study demonstrated that the proportion of Spanish minors who meet with all the 24-h movement guidelines is low. Furthermore, it could be relevant to the promotion of the 24-h movement guidelines to prevent the risk of socioemotional behavioral problems., (© 2022 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Introduction: The multiple benefits of physical activity (PA) compared to the current lack of adherence to this behavior in older people makes it necessary to identify the factors related to its long-term dropout, therefore, the aim of this study was: (i) to study the evolution of behavior change for PA through stages of change (SoC) after 8 years and, to identify the associated factors related to the worsening of SoC for PA., Methods: A total of 714 Spanish older adults (>65 years) participated in the Longitudinal elderly EXERNET study 8 years follow-up. SoC for PA from Transtheoretical model of behavior change (TTM), body composition [BMI, fat mass, lean mass, waist circumference (WC), and hip circumference (HC)] and physical fitness (EXERNET battery fitness tests) were recorded. A multivariate binary logistic regression model was used to identify the potential predictive factors of worsening SoC for PA., Results: Three hundred and sixty participants (50.4%) worsening their SoC for PA after 8 years. Predictors factors associated with worsening of SoC were: HC (OR = 1.022; 95% CI: 1.001, 1.044), Lower body strength (OR = 0.940; 95% CI: 0.887, 0.997) and aerobic endurance at the 6 min-walk test (OR = 0.997; 95% CI: 0.995, 0.999)., Conclusion: This study highlights that we need to identify adults with high HC, lower body strength and lower aerobic endurance to design a tailored PA program. Identifying the determinants of losing adherence to PA will help in the creation, design, and evaluation of exercise programs with the goal of reducing older adults' drop-outs rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiménez-Zazo, Hernández-Martínez, Romero-Blanco, Cabanillas, Pérez-Gómez, Ara, Casajús, Vicente-Rodríguez, Gesteiro, González-Gross and Aznar.)

The aim of this study was to explore the differences among between adherence to physical activity (PA) and sociodemographic variables, body composition, and physical fitness levels in older adults (>65 years). A number of 2712 participants (2086 female; 76.92%) ranging from 65 to 92 years, participated in the study. Stages of change (SoC) for PA from the transtheoretical model of change (TTM), together with different sociodemographic variables, physical fitness tests (Senior Fitness Test), and waist and hip circumferences were evaluated. Significant differences were found in age, gender, educational level, current income, physical fitness test, and body composition (all of them, p < 0.05), according to the different SoC. Greater adherence to PA practice (action and maintenance stages) was related to better academic level, higher economic income, the male gender, better results in the physical fitness test, and healthier anthropometrics perimeters. Future research is needed to identify the relationship between these variables longitudinally.

A progressive shift away from traditional healthy dietary patterns, such as the Mediterranean diet (MedDiet), has been observed in recent decades. The aim of this study was to assess determinants of optimal adherence to the MedDiet in Spanish children and adolescents. A cross-sectional analysis was included in the PASOS nationwide representative study in Spain. Participants were 3607 children and adolescents; 8-16 years old. Primary and secondary outcome measures of weight and height were measured. Adherence to the MedDiet, physical activity, and sedentary behavior in children and adolescents, as well as parental physical activity and dietary habits, were assessed. Optimal adherence to the MedDiet was observed in 45.5% of primary school students and 34.8% of secondary school students (OR: 0.65; 95%CI: 0.56-0.75). Optimal adherence to the MedDiet was higher in children/adolescents meeting daily recommended moderate and vigorous physical activity (OR: 2.39, 95%CI: 1.97-2.89) and in those meeting daily recommended screen time on weekdays (OR: 2.05, 95%CI: 1.77-2.38) and weekends (OR: 1.76, 95%CI: 1.48-2.10). Participants with optimal adherence to the MedDiet were more likely to have mothers with a high-level education and high-tercile of SDQS, mothers who never smoked or were former smokers, and mothers who met the recommended physical activity and screen time. It can be concluded that a low prevalence of optimal adherence to the MedDiet was found among current Spanish children and adolescents. Optimal adherence to the MedDiet was associated with reaching the recommendations on physical activity and screen time, with the highest maternal educational level, and healthier maternal lifestyles.

Background and Aims: The World Health Organization recommended simultaneous measurement of body mass index (BMI) and waist circumference (WC) and suggested joint use to predict disease risks. The aim of this study was to assess the prevalence of BMI and waist-to-height ratio (WHtR) categories among Spanish children and adolescents, as well as their associations with several lifestyle factors., Methods: Cross-sectional analysis of 8-16-year-old children and adolescents ( n = 3772) were included in the PASOS nationwide representative study. Children/adolescents and their mothers/female caregivers answered a questionnaire on lifestyle and health factors. Child/adolescent anthropometrics were measured. Four combined BMI-WHtR disease risk categories were built., Results: A third of participants showed combined BMI-WHtR categories with high disease risk (12.3% 'increased risk', 9.7% 'high risk', 14.3% 'very high risk'). Participants in the 'very high risk' group were less likely to be females (odds ratio 0.63; 95% CI: 0.52-0.76) and adolescents (0.60; 95% CI: 0.49-0.72), to practice ≥60 min/day of moderate-vigorous physical activity (MVPA) (0.73; 95% CI: 0.57-0.93), and to watch <120 min/day of total screen time on weekdays (0.61; 95% CI: 0.49-0.76). Mothers of participants in the 'very high risk' group were less likely to have a high educational level, be in the overweight or normal range, have never smoked or were former smokers, and watch <120 min/day of total screen time on weekends. Participants in the 'increased' and 'high risk' categories had mothers with normal weight and ≥60 min/day of MVPA. Participants in the 'high risk' group did not achieve ≥60 min/day of MVPA and showed lower adherence to the Mediterranean diet., Conclusions: Adherence to a healthy lifestyle in children and adolescents, but also in their mothers/female caregivers during offspring's childhood and adolescence, is associated with low BMI-WHtR disease risk.

Familial Parkinson disease (PD) is associated with rare genetic mutations, but the etiology in most patients with sporadic (s)PD is largely unknown, and the basis for its progression to dementia (sPDD) is poorly characterized. We have identified that loss of IFNβ or IFNAR1, the receptor for IFNα/β, causes pathological and behavioral changes resembling PDD, prompting us to hypothesize that dysregulated genes in IFNβ-IFNAR signaling pathway predispose one to sPD. By transcriptomic analysis, we found defective neuronal IFNβ-IFNAR signaling, including particularly elevated PIAS2 associated with sPDD. With meta-analysis of GWASs, we identified sequence variants in IFNβ-IFNAR-related genes in sPD patients. Furthermore, sPDD patients expressed higher levels of PIAS2 mRNA and protein in neurons. To determine its function in brain, we overexpressed PIAS2 under a neuronal promoter, alone or with human α-synuclein, in the brains of mice, which caused motor and cognitive impairments and correlated with intraneuronal phosphorylated (p)α-synuclein accumulation and dopaminergic neuron loss. Ectopic expression of neuronal PIAS2 blocked mitophagy, increased the accumulation of senescent mitochondrial and oxidative stress, as evidenced by excessive oxDJ1 and 8OHdG, by inactivating ERK1/2-P53 signaling. Conversely, PIAS2 knockdown rescued the clinicopathological manifestations of PDD in Ifnb -/- mice on restoring mitochondrial homeostasis, oxidative stress, and pERK1/2-pP53 signaling. The regulation of JAK-STAT2-PIAS2 signaling was crucial for neurite outgrowth and neuronal survival and excitability and thus might prevent cognitive impairments. Our findings provide insights into the progression of sPD and dementia and have implications for new therapeutic approaches., (© 2021. The Author(s).)

Environmental factors play an important role in obesity-related behaviors. Evidence indicates significant associations between weight and urban green spaces in adults, but it is not clear whether this relationship applies to adolescents. Therefore, our aim was to determine the associations between urban green spaces, greenness exposure and species richness in residential environments with physical activity and body mass index. Sixty-two adolescents between 12 and 18 years of age answered a self-administered questionnaire, providing information on height, weight, age, sex and home address. Data on socioeconomic deprivation were obtained from the European Index of Deprivation for Small Portuguese Areas. Physical activity levels were assessed using accelerometers. Urban green space counts and the normalized difference vegetation index values were measured using buffers along the roads with distances of 300, 500, 1000 and 1500 m from each participant's residence. To quantify the species richness, the species richness index was used. Linear regression models were fitted to analyze whether urban green spaces, exposure to green spaces and species richness counts for each distance were associated with physical activity and self-reported body mass index. We did not find significant associations between the independent variables and the probability of overweight or obesity. The relationship between environmental variables, adolescents' physical activity and body weight seems to be complex and further studies may contribute to better understanding of the topic., Competing Interests: The authors declare no conflict of interest.

Active commuting to school in children and adolescents can help achieve compliance with the World Health Organization (WHO) recommendations for physical activity. This study aimed to evaluate the relationship between the mode of transport used to go to school and the mode of transport used to go to extracurricular sports practice. Multistage random cluster sampling was conducted to include 128 schools with the participation of 11,017 students between the ages of 5 and 19. Participants completed the survey of sports habits designed by the National Sports Council. The results revealed that the mode of transport used to go to school is significantly related to the mode of transport used to go to sports practice. A total of 54.3% of students aged 5 to 19 years walk to school. A total of 23.7% of boys walk and 7.9% bike to extracurricular physical activities vs. 24.1% of girls who walk. The fact that girls only walk to extracurricular physical activities implies that the organized sports activities were nearby. Therefore, it seems crucial to have a wide range of physical activities on offer locally to promote extracurricular physical activity participation for girls.

During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain "ad hoc" questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease leading to damage of white matter (WM) and grey matter (GM). Magnetic resonance imaging (MRI) is the modality of choice to assess brain damage in MS, but there is an unmet need in MRI for achieving higher sensitivity and specificity to MS-related microstructural alterations in WM and GM., Objective: To explore whether tensor-valued diffusion MRI (dMRI) can yield sensitive microstructural read-outs for focal demyelination in cerebral WM and deep GM (DGM)., Methods: Eight rats underwent L-α-Lysophosphatidylcholine (LPC) injections in the WM and striatum to introduce focal demyelination. Multimodal MRI was performed at 7 Tesla after 7 days. Tensor-valued dMRI was complemented by diffusion tensor imaging, quantitative MRI and proton magnetic resonance spectroscopy (MRS)., Results: Quantitative MRI and MRS confirmed that LPC injections caused inflammatory demyelinating lesions in WM and DGM. Tensor-valued dMRI illustrated a significant decline of microscopic fractional anisotropy (µFA) in both LPC-treated WM and DGM (P < 0.005) along with a marked increase of isotropic kurtosis (MK I ) in DGM (P < 0.0001)., Conclusion: Tensor-valued dMRI bears considerable potential for microstructural imaging in MS, suggesting a regional µFA decrease may be a sensitive indicator of MS lesions, while a regional MK I increase may be particularly sensitive in detecting DGM lesions of MS., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: We hypothesize alterations in the quality and quantity of anti-43-kDa TAR DNA-binding protein (TDP-43) naturally occurring autoantibodies (NAbs) in patients with amyotrophic lateral sclerosis (ALS); therefore, we assessed relative binding properties of anti-TDP-43 NAbs composite in plasma from patients with ALS in comparison with healthy individuals., Methods: ELISA competition assay was used to explore the apparent avidity/affinity of anti-TDP-43 NAbs in plasma from 51 normal controls and 30 patients with ALS. Furthermore, the relative levels of anti-TDP-43 NAbs within the immunoglobulin (Ig) classes of IgG (isotype IgG1-4) and IgMs were measured using classical indirect ELISA. The occurring results were hereafter correlated with the measures of disease duration and disease progression., Results: High-avidity/affinity anti-TDP-43 NAbs levels were significantly reduced in plasma samples from patients with ALS. In addition, a significant decrease in relative levels of anti-TDP-43 IgG3 and IgM NAbs and a significant increase in anti-TDP-43 IgG4 NAbs were observed in ALS plasma vs controls. Furthermore, a decrease in global IgM and an increase in IgG4 levels were observed in ALS. These aberrations of humoral immunity correlated with disease duration, but did not correlate with ALS Functional Rating Scale-Revised scores., Conclusions: Our results may suggest TDP-43-specific immune aberrations in patients with ALS. The skewed immune profiles observed in patients with ALS could indicate a deficiency in the clearance capacity and/or blocking of TDP-43 transmission and propagation. The decrease in levels of high affinity/avidity anti-TDP-43 NAbs and IgMs correlates with disease progression and may be disease predictors., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Healthy aging makes the practice of physical activity (PA) a necessity. However, PA guidelines achievement in older adults is scarce. The use of behavioral theories such as Transtheoretical Model (TTM), helps in older adults PA promotion. The aim of this review was to identify the use of TTM for PA in older adults (>60 years). PubMed, SPORTdiscus, and Medline databases were used to conduct the search. All steps of the process followed the recommendations of the PRISMA flow-diagram. We identified eight studies: Six were descriptive cross-sectional studies, one prospective-cohort study and one with a quasi-experimental design. Only two papers evaluated the four behavior change dimensions within the same study, three evaluated the processes of change and the decisional balance, four evaluated the exercise self-efficacy and all assessed the stages of change for PA behavior. From this review, we can conclude that TTM is a useful and suitable behavior model in creating, developing, and evaluating interventions with the aim of acquiring and improving PA habits in the older adults. However, there is paucity of research in this area, and more studies including the four behavioral change dimensions are needed to analyze the effect of TTM on the promotion of PA in the older adults.

Over 70 million European pregnant women are smokers during their child-bearing years. Consumption of tobacco-containing products during pregnancy is associated with several negative behavioral outcomes for the offspring, including a higher susceptibility for the development of attention-deficit/hyperactive disorder (ADHD). In efforts to minimize fetal exposure to tobacco smoke, many women around the world switch to nicotine replacement therapies (NRTs) during the gestational period; however, prenatal nicotine exposure (PNE) in any form has been associated with alterations in cognitive processes, including learning, memory, and attention. These processes are controlled by glutamatergic signaling of hippocampal pyramidal neurons within the CA1 region, suggesting actions of nicotine on glutamatergic transmission in this region if present prenatally. Accordingly, we aimed to investigate hippocampal glutamatergic function following PNE treatment in NMRI mice employing molecular, cellular electrophysiology, and pharmacological approaches, as well as to evaluate cognition in the rodent continuous performance task (rCPT), a recently developed mouse task allowing assessment of learning, attention, and impulsivity. PNE induced increases in the expression levels of mRNA coding for different glutamate receptors and subunits within the hippocampus. Functional alterations in AMPA and NMDA receptors on CA1 pyramidal neurons of PNE mice were suggestive of higher GluA2-lacking and lower GluN2A-containing receptors, respectively. Finally, PNE was associated with reduced learning, attention, and enhanced impulsivity in the rCPT. Alterations in glutamatergic functioning in CA1 neurons parallel changes seen in the spontaneously hypertensive rat ADHD model and likely contribute to the lower cognitive performance in the rCPT.

Background: Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe., Methods: Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2-18 years) from 18 different European countries., Results: Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age., Conclusions: Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.

Disruption of sensorimotor gating causes "flooding" of irrelevant sensory input and is considered a congenital trait in several neurodevelopmental disorders. Prepulse inhibition of acoustic startle response (PPI) is the operational measurement and has a high translational validity. Pharmacological studies in rodents have linked alterations in serotonin, dopamine and glutamate signalling to PPI disruption. How PPI response is associated with gene expression levels of these receptors is unknown. PPI response was assessed in 39 genetically heterogeneous National Institutes of Health-Heterogeneous Stock (NIH-HS) rats. Animals were classified as high, medium or low PPI. Expression levels of glutamate metabotropic receptor 2 (Grm2), dopamine receptor D2 (Drd2), dopamine receptor D1 (Drd1), serotonin receptor 1A (Htr1a), serotonin receptor 2A (Htr2a) and homer scaffolding protein 1 (Homer1) were investigated in prefrontal cortex (PFC) and striatum (STR). When comparing the two extreme phenotypes, only Drd2 in STR showed increased expression in the low PPI group. A multinomial model fitting all genes and all groups indicated that Grm2 in PFC, and Grm2 and Drd2 in the STR predicted PPI group. This was corroborated by a linear relationship of Grm2 with PPI in PFC, and Drd2 with PPI in STR. An interaction between levels of H3K27 trimethylation, associated with transcriptional repression, and PPI phenotype was observed for Drd2 in STR. Gene set enrichment analysis on a microarray dataset on Lewis rats confirmed enrichment of Drd2 in PFC in relation to PPI. These findings contribute to the understanding of the genetic substrate behind alterations in sensorimotor gating, relevant for its linkage to neurodevelopmental disorders.

Accumulating evidence suggests neuroinflammation to be an integrated feature of neurodegeneration. Profiling inflammatory mediators across diseases may reveal common and disease-specific signatures. Here, we focused on progressive supranuclear palsy (PSP), a tauopathy presenting motor and cognitive dysfunction. We screened for 21 cytokines and growth factors in the dorsomedial prefrontal cortex of 16 PSP and 16 control brains using different quantitative techniques. We found and validated increased interleukin (IL)-2 protein levels in the PSP group expressed locally by neurons and glia cells. We further investigated central players in neuroinflammatory pathways and found increased mRNA expression of glycogen synthase kinase 3 beta (GSK3B). IL-2 and GSK3B proteins are T and natural killer (NK) cell regulators and have previously been associated with other neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple system atrophy. In addition, we identified a shift in peripheral CD4 + and CD8 + T cell populations toward increased numbers of memory and reduced numbers of naive T cells. We also observed increased numbers of CD56 + NK cells, but not of CD56 + CD57 + or CD57 + NK cells. Our findings suggest a role for IL-2 in PSP disease processes and point toward active and possibly dysfunctional peripheral immune responses in these patients.

Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca 2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca 2+ levels followed by a later Ca 2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro , and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca 2+ CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies. We conclude that α-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA activity is neuroprotective, indicating that SERCA and down-stream processes may be therapeutic targets for treating α-synucleinopathies., (© 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

The serotonin 2A (5-HT 2A ) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT 2A and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors. The striatum (STR) was included in the analysis. 5-HT 2A , 5-HT 1A , and mGlu2 mRNA and [ 3 H]ketanserin binding levels were measured in brain homogenates. As expected, 5-HT 2A binding was significantly increased in PFC in the RHA-I rats, while no difference in binding was observed in STR. Surprisingly, 5-HT 2A gene expression was unchanged in PFC but significantly decreased in STR. mGlu2 receptor gene expression was significantly decreased in both PFC and STR. No differences were observed for the 5-HT 1A receptor. Chromatin immunoprecipitation assay revealed increased trimethylation of histone 3 at lysine 27 (H3K27me3) at the promoter region of the HTR2A gene in the STR. We further looked at the Akt/GSK3 signaling pathway, a downstream point of convergence of the serotonin and glutamate system, and found increased phosphorylation levels of GSK3β at tyrosine 216 and increased β-catenin levels in the PFC of the RHA-I rats. These results reveal region-specific regulation of the 5-HT 2A receptor in the RHA-I rats probably due to absence of mGlu2 receptor that may result in differential regulation of downstream pathways.

Executive function entails the interplay of a group of cognitive processes enabling the individual to anticipate consequences, attain self-control, and undertake appropriate goal-directed behaviour. Serotonin signalling at serotonin 2A receptors (5-HT2AR) has important effects on these behavioural and cognitive pathways, with the prefrontal cortex (PFC) as the central actor. Indeed, the 5-HT2ARs are highly expressed in PFC, where they modulate cortical activity and local network oscillations (brain waves). Numerous psychiatric and neurodegenerative diseases result in disrupted executive function. Animal and human studies have linked these disorders with alterations in the 5-HT2AR system, making this an important pharmacological target for the treatment of disorders with impaired cognitive function. This review aims to describe the current state of knowledge on the role of 5-HT2AR signalling in components of executive function, and how 5-HT2AR systems may relate to executive dysfunctions occurring in psychiatric and neurodegenerative diseases. We hope thereby to provide insight into how pharmacotherapy targeting the 5-HT2AR may ameliorate (or exacerbate) aspects of these disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Physical activity (PA) is recommended as part of the treatment regimen for cystic fibrosis (CF) although objective methods have been scarcely used to monitor achievement of PA guidelines., Methods: PA was measured by accelerometer in outpatient CF children (n=47) and results were compared with those obtained in age- and gender-matched healthy controls (n=39)., Results: 2.1% of the outpatients fulfilled PA guidelines (i.e. ≥60min·day(-1) of moderate-to-vigorous PA (MVPA)) vs. 34.2% of controls. Overall, lower MVPA levels were observed in CF patients than controls despite the former undergoing more light or total PA. Peak oxygen uptake was also lower in the CF group than in controls (37.5±7.8 vs. 43.5±7.6ml·kg(-1)·min(-1), p=0.002) and was correlated with MVPA and vigorous PA in the former., Conclusions: These findings support a need to promote PA interventions (including MVPA) targeted at improving cardiorespiratory fitness in CF children., (© 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.)

The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

The serotonergic transmitter system regulates hippocampal activity through its raphe projection to hippocampus and medial septum/diagonal band of Broca complex (MS/DBB), and most likely also indirectly through its interaction with the cholinergic neurotransmitter system. Nicotine, e.g., enhances hippocampal serotonin release probably through presynaptic nicotinic receptors. We investigated the possible presence of the alpha 7-nicotinic subunit on serotonergic neurons projecting to hippocampus and MS/DBB. By retrograde neuronal tracing, hippocampal serotonergic neurons were identified and with double fluorescence immunostaining and Alexa-488 bound alpha-bungarotoxin the presence of active alpha 7 receptor on their soma was determined. Most of the retrogradely labeled serotonin neurons contained the alpha 7 subunit. A low degree of colocalization between alpha-bungarotoxin and serotonin-positive neurons suggest that the alpha 7 subunit may be transported anterogradely to the serotonergic axonal terminals.