Los niños prematuros tienen mayor riesgo de presentar dificultades cognitivas, motoras y de comportamiento

Cognitive, motor, behavioural and academic performances of children born preterm: a meta‐analysis and systematic review involving 64 061 children

Abstract

Background

Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy.

Objective

To quantify the long‐term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term‐born children.

Search strategy

PubMed and Embase were searched from January 1980 to December 2016 without language restrictions.

Selection criteria

Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term‐born cohort.

Data collection and analysis

We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model.

Main results

We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: −0.70; 95% CI: −0.73 to −0.66), PIQ (SMD: −0.67; 95% CI: −0.73 to −0.60) and VIQ (SMD: −0.53; 95% CI: −0.60 to −0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38–48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3–1.8), with a differential effect observed according to the severity of prematurity (I2 = 49.4%, P = 0.03).

Conclusions

Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children.

Videojuegos de acción para tratar la dislexia

Enhancing reading performance through action video games: the role of visual attention span

Abstract

Recent studies reported that Action Video Game-AVG training improves not only certain attentional components, but also reading fluency in children with dyslexia. We aimed to investigate the shared attentional components of AVG playing and reading, by studying whether the Visual Attention (VA) span, a component of visual attention that has previously been linked to both reading development and dyslexia, is improved in frequent players of AVGs. Thirty-six French fluent adult readers, matched on chronological age and text reading proficiency, composed two groups: frequent AVG players and non-players. Participants performed behavioural tasks measuring the VA span, and a challenging reading task (reading of briefly presented pseudo-words). AVG players performed better on both tasks and performance on these tasks was correlated. These results further support the transfer of the attentional benefits of playing AVGs to reading, and indicate that the VA span could be a core component mediating this transfer. The correlation between VA span and pseudo-word reading also supports the involvement of VA span even in adult reading. Future studies could combine VA span training with defining features of AVGs, in order to build a new generation of remediation software.

Introduction

Action video games (AVGs) and books

Efecto de la musicoterapia como terapia no farmacológica en la enfermedad de Alzheimer

Music therapy as a non-pharmacological treatment in Alzheimer's disease. A systematic review

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease which involves, among other manifestations, a progressive deterioration of memory and language, as well as behavioral disorders. In addition to non-curative pharmacological therapies, for the last years, music therapy has been developed as an effective non-pharmacological therapy in order to relieve many of these manifestations.To analyze the recent scientific evidence about the effect of music therapy on cognitive and behavioral symptoms in patients with AD.A systematic review has been carried out by means of a bibliographical research using the database PubMed and Science Direct. The key words used for this search were 'Alzheimer's disease' and 'music therapy', as well as the boolean operator 'AND'. We selected those publications between January 2006 and December 2016 and after inclusion criteria, 21 publications were selected.This systematic review has demonstrated the beneficial impact of music therapy on cognition (memory, attention, language), emotion and behavior (anxiety, depression and agitation) in AD patients.Music therapy constitutes a non-pharmacological therapy effective for some cognitive, emotional and behavioral symptoms in patients with AD. However, further investigations and more evidence in this field are needed to claim conclusively the impact of music therapy on this disease.

El trasplante de ambas manos provoca el remapeo del cerebro

Massive cortical reorganization is reversible following bilateral transplants of the hands: evidence from the first successful bilateral pediatric hand transplant patient

Abstract

In this repeated measures case study, we show that sensory deafferentation after limb amputation leads to changes in cortical somatotopic maps which are reversible after restoration of sensory input. Using magnetoencephalography (MEG), we observed in a child with bilateral hand transplants large‐scale shifts in somatosensory lip cortical representation from anatomic hand area to anatomic face region. After recovery of tactile sensation in the digits, responses to finger stimulation were localized to orthotopic sensory cortex, but with atypical electrophysiologic features (amplitude and frequencies).

Introduction

Loss of peripheral sensory inputs leads to functional reorganization of primary somatosensory cortex.1-3 Following deafferentation of the upper limb in adult primates, the area of somatosensory cortex deprived of afferent signals begins to respond to tactile stimulation of the face, a massive cortical reorganization (MCR) mediated subcortically through the cuneate nucleus.4 Similar demonstrations of MCR have also been reported in human adults with unilateral upper limb amputations using MEG.5-7 MCR has not been demonstrated in children previously, and the cortical adaptation to restoration of sensory inputs in children is unknown. We utilized the spatial and temporal resolution of MEG measurements of tactile sensory responses to provide insight into the dynamics of sensory reorganization and to ask, can massive reorganization of primary somatosensory cortex after early‐life limb loss revert to a typical somatotopic map after hand transplantation in a child?

MEG somatosensory responses and index finger touch sensitivity (using monofilament testing) were recorded over the year following transplantation at visits: 1 (6 weeks), 2 (18 weeks), 3 (33 weeks), and 4 (54 weeks). We sought to determine whether (1) MCR of face to hand area was present during the prerecovery period, (2) MCR would revert to typical orthotopic somatosensory locations with recovery of sensory function of the hands, and (3) somatosensory responses from tactile stimulation of transplanted fingers differ from age‐matched controls.

Un proceso reactivo en las células nerviosas podría contribuir al desarrollo de enfermedad de Parkinson

S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson’s Disease Models

Summary

Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson’s disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity. SNO-PINK1 decreases Parkin translocation to mitochondrial membranes, disrupting mitophagy in cell lines and human-iPSC-derived neurons. We find levels of SNO-PINK1 in brains of α-synuclein transgenic PD mice similar to those in cell-based models, indicating the pathophysiological relevance of our findings. Importantly, SNO-PINK1-mediated deficits in mitophagy contribute to neuronal cell death. These results reveal a direct molecular link between nitrosative stress, SNO-PINK1 formation, and mitophagic dysfunction that contributes to the pathogenesis of PD.

Graphical Abstract

Efecto de la cocaína sobre la inhibición por prepulso de la respuesta de sobresalto

Effects of cocaine on prepulse inhibition of the startle response

Abstract

Prepulse inhibition (PPI) of the startle response is an index used to evaluate how the pre-attention system works. PPI is altered in patients with a mental disorder such as schizophrenia and in subjects who are vulnerable to it. Likewise, cocaine users also frequently exhibit psychiatric disorders as schizophrenia.To know the alterations that cocaine produces on PPI.A comprehensive review is carried out, covering both clinical and preclinical studies with animal models that have evaluated the effects of cocaine exposure on the PPI paradigm. Underlying neural bases and mechanisms of action are suggested to explain these findings.Cocaine alters PPI through its action on the dopaminergic system. Acute exposure of cocaine decreases PPI by increasing dopamine, while with chronic use, depending on withdrawal time, PPI can be restored. However, the effects of cocaine on PPI appear to depend on the baseline levels of PPI shown by the individual. Thus, since a deficit in PPI has been associated with a greater vulnerability to developing mental pathologies such as schizophrenia, PPI level in subjects could be considered as a biomarker of psychiatric vulnerability. Therefore, a better understanding of the effect of drugs such as cocaine on PPI may help to understand the development of dual pathology.

Describen un nuevo proceso biológico de la enfermedad de Alzheimer

Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo

Abstract

Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles. Despite the increase in neurofibrillary tangles, TIA1 reduction increased neuronal survival and rescued behavioral deficits and lifespan. These data provide in vivo evidence that TIA1 plays a key role in mediating toxicity and further suggest that RBPs direct the pathway of tau aggregation and the resulting neurodegeneration. We propose a model in which dysfunction of the translational stress response leads to tau-mediated pathology.

Trastornos neurológicos derivados del virus del Zika podrían deberse a la respuesta inmunitaria

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

Abstract

Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly1 and Guillain–Barré syndrome2,3 as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis4, meningoencephalitis5 and fatal encephalitis6. Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1−/−) mice, an infection model that exhibits high viral burden within the central nervous system. We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1deficiency in the haematopoietic compartment. However, spread of ZIKV within the central nervous system is supported by Ifnar1-deficient non-haematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood–brain barrier and a large influx of CD8+ effector T cells. We also find that antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but, as a consequence, instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV neuropathogenesis within a susceptible mouse model and suggests blood–brain barrier breakdown and T-cell-mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.

Desmontan científicamente la teoría mitocondrial del envejecimiento en deportistas de élite

Antioxidant effect of exercise: Exploring the role of the mitochondrial complex I superassembly

Abstract

Mitochondrial respiratory complexes become assembled into supercomplexes (SC) under physiological conditions. One of the functional roles of these entities is the limitation of reactive oxygen species (ROS) produced by complex I (CI) of the respiratory chain. We sought to determine whether the systemic antioxidant effect of exercise is mediated by the assembly of mitochondrial CIs into SCs in rats. Male Wistar rats were exercise trained or remained sedentary for ten weeks; then, blood samples were collected, and the gastrocnemius muscle was isolated. The assembly of mitochondrial SCs and the lipid peroxidation of the mitochondrial and plasmaticfractions were assessed. Our results demonstrate that exercise induced the assembly of CI into SCs in the gastrocnemius and induced a systemic decrease in lipid peroxidation. We also found an inverse association between the superassembly of CIs and mitochondrial lipid peroxidation (p < 0.01) and protein carbonyls (p < 0.05). We conclude that exercise induces the chronic assembly of CIs into SCs, which provide mitochondrial protection against oxidative damage, at least in the studied muscle. Given the relevant role that mitochondria play in health and disease, these findings should help to elucidate the role of exercise as a therapeutic approach for metabolic diseases.

Graphical abstract

Analizan en un modelo animal la influencia del estrés social en el efecto reforzante del éxtasis

The influence of social stress on the reinforcing effect of ecstasy under the conditioned place preference paradigm: the role played by age, dose and type of stress

Abstract

Addiction to drugs is a chronic illness with severe repercussions for those that consume them and to date has no known cure. Psychostimulants, such as ecstasy, are the most widely consumed illegal drugs among adolescents and young adults.To describe and to analyse the different variables that can influence the effects of social stress and the reinforcing properties of ecstasy. Likewise, it also seeks to evaluate whether the effects of social stress on conditioned place preference (induced by ecstasy) are similar to those deriving from other psychostimulants, such as cocaine.Social defeat evaluated in the short term has an effect only on adult animals by diminishing sensitivity to the conditioned reinforcing effects of ecstasy. Conversely, long-term social stress increases the reinforcing effects of this drug in adolescent and adult animals. The dose of ecstasy employed has little influence on the effects of social defeat on conditioned place preference. In comparison to the effects of social stress on the reinforcing properties of cocaine, a different effect is only observed when defeat is evaluated in the short term.Different variables modulate the reinforcing effects of ecstasy, such as the age of the animals, the dose employed or exposure to stress. It is essential to study these variables in order to determine the neurobiological and environmental vulnerability factors that can have an influence on the development of addiction to ecstasy.

La metformina se asocia con una mejor función cognitiva en pacientes con enfermedad de Huntington

Metformin intake associates with better cognitive function in patients with Huntington's disease

Abstract

Huntington’s disease (HD) is an inherited, dominant neurodegenerative disorder caused by an abnormal expansion of CAG triplets in the huntingtin gene (htt). Despite extensive efforts to modify the progression of HD thus far only symptomatic treatment is available. Recent work suggests that treating invertebrate and mice HD models with metformin, a well-known AMPK activator which is used worldwide to treat type 2-diabetes, reduces mutant huntingtin from cells and alleviates many of the phenotypes associated to HD. Herein we report statistical analyses of a sample population of participants in the Enroll-HD database, a world-wide observational study on HD, to assess the effect of metformin intake in HD patients respect to cognitive status using linear models. This cross-sectional study shows for the first time that the use of metformin associates with better cognitive function in HD patients.

La apnea del sueño podría aumentar el riesgo de enfermedad de Alzheimer

Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study

Abstract

Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer’s disease. However, how sleep apnea affects longitudinal risk for Alzheimer’s disease is less well understood.

Objectives: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly.

Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device.

Measurements and Main Results: We found that severity of OSA indices (AHIall [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively).

Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

Keywords: obstructive sleep apnea; amyloid burden; Pittsburgh compound B positron emission tomography scan; cerebrospinal fluid amyloid β; cognitive impairment

Nuevo mecanismo para entender mejor la enfermedad de Parkinson

αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease

Abstract

The etiology of Parkinson’s disease (PD) converges on a common pathogenic pathway of mitochondrial defects in which α-Synuclein (αSyn) is thought to play a role. However, the mechanisms by which αSyn and its disease-associated allelic variants cause mitochondrial dysfunction remain unknown. Here, we analyzed mitochondrial axonal transport and morphology in human-derived neurons overexpressing wild-type (WT) αSyn or the mutated variants A30P or A53T, which are known to have differential lipid affinities. A53T αSyn was enriched in mitochondrial fractions, inducing significant mitochondrial transport defects and fragmentation, while milder defects were elicited by WT and A30P. We found that αSyn-mediated mitochondrial fragmentation was linked to expression levels in WT and A53T variants. Targeted delivery of WT and A53T αSyn to the outer mitochondrial membrane further increased fragmentation, whereas A30P did not. Genomic editing to disrupt the N-terminal domain of αSyn, which is important for membrane association, resulted in mitochondrial elongation without changes in fusion-fission protein levels, suggesting that αSyn plays a direct physiological role in mitochondrial size maintenance. Thus, we demonstrate that the association of αSyn with the mitochondria, which is modulated by protein mutation and dosage, influences mitochondrial transport and morphology, highlighting its relevance in a common pathway impaired in PD.

Vinculan el consumo de paracetamol durante el embarazo con el riesgo de TDAH de los niños

Deterioro cognitivo como factor independiente de riesgo hospitalario

Cognitive impairment as a predictor of functional decline after hospitalization: DECOFIRH Study

Abstract

Cognitive impairment is underdiagnosed in the elderly. We aimed to study the rate of positive responses to an informant-based questionnaires and functional disability after hospital discharge.Observational prospective case series of patients aged 70-85 years-old admitted for hospitalization in an Internal Medicine ward. All medical records were reviewed and those patients with no previous diagnosis of dementia or related neurological conditions, no previous recent hospitalization or not having a caregiver were evaluated after signing an informed consent. A medical interview including the Alzheimer's Disease 8 (AD8), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Barthel Index was completed. Barthel Index was obtained three months after discharge.During a 3-month period a total of 809 admissions were screened and 79 (9.7%) fulfilled the study criteria. Patient's mean age was 80 years-old. Common comorbidities were arterial hypertension (83.5%), major surgery (54.4%) and heart disorders (50.6%). The most frequent cause of admission was infectious disease (37.9%). Test positivity for cognitive impairment was 30.3% for IQCODE and 34.1% for AD8. At admission 37.9% of the patients were functionally independent. At three months this percentage dropped to 24%.In this small sample size, almost a third of older patients, without major comorbidities or neurological disorders, admitted to a general hospital showed an informant-based suggestion of cognitive impairment previously undiagnosed. Functional impairment affects almost a quarter of these patients three months after admission.

Vivir cerca de espacios verdes se asocia con una mayor capacidad de atención de los niños

Lifelong Residential Exposure to Green Space and Attention: A Population-based Prospective Study

BACKGROUND:

Natural environments, including green spaces, may have beneficial impacts on brain development. However, longitudinal evidence of an association between long-term exposure to green spaces and cognitive development (including attention) in children is limited.

OBJECTIVES:

We evaluated the association between lifelong residential exposure to green space and attention during preschool and early primary school years.

METHODS:

This longitudinal study was based on data from two well-established population-based birth cohorts in Spain. We assessed lifelong exposure to residential surrounding greenness and tree cover as the average of satellite-based normalized difference vegetation index and vegetation continuous fields, respectively, surrounding the child’s residential addresses at birth, 4–5 y, and 7 y. Attention was characterized using two computer-based tests: Conners’ Kiddie Continuous Performance Test (K-CPT) at 4–5 y (n=888) and Attentional Network Task (ANT) at 7 y (n=987). We used adjusted mixed effects models with cohort random effects to estimate associations between exposure to greenness and attention at ages 4–5 and 7 y.

RESULTS:

Higher lifelong residential surrounding greenness was associated with fewer K-CPT omission errors and lower K-CPT hit reaction time-standard error (HRT-SE) at 4–5 y and lower ANT HRT-SE at 7 y, consistent with better attention. This exposure was not associated with K-CPT commission errors or with ANT omission or commission errors. Associations with residential surrounding tree cover also were close to the null, or were negative (for ANT HRT-SE) but not statistically significant.

CONCLUSION:

Exposure to residential surrounding greenness was associated with better scores on tests of attention at 4–5 y and 7 y of age in our longitudinal cohort. https://doi.org/10.1289/EHP694

Diagnóstico precoz de la dislexia a través de las capacidades auditivas

The Role of Slow Speech Amplitude Envelope for Speech Processing and Reading Development

This study examined the putative link between the entrainment to the slow rhythmic structure of speech, speech intelligibility and reading by means of a behavioral paradigm. Two groups of 20 children (Grades 2 and 5) were asked to recall a pseudoword embedded in sentences presented either in quiet or noisy listening conditions. Half of the sentences were primed with their syllabic and prosodic amplitude envelope to determine whether a boost in auditory entrainment to these speech features enhanced pseudoword intelligibility. Priming improved pseudoword recall performance only for the older children both in a quiet and a noisy listening environment, and such benefit from the prime correlated with reading skills and pseudoword recall. Our results support the role of syllabic and prosodic tracking of speech in reading development.

Aumenta la prevalencia de factores de riesgo vascular en pacientes con ictus isquémico

Increasing prevalence of vascular risk factors in patients with stroke: A call to action.

Abstract

Objective: To evaluate trends in prevalence of cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and drug abuse) and cardiovascular diseases (carotid stenosis, chronic renal failure [CRF], and coronary artery disease [CAD]) in acute ischemic stroke (AIS) in the United States.

Methods: We used the 2004–2014 National Inpatient Sample to compute weighted prevalence of each risk factor in hospitalized patients with AIS and used joinpoint regression to evaluate change in prevalence over time.

Results: Across the 2004–2014 period, 92.5% of patients with AIS had ≥1 risk factor. Overall age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively, while those of carotid stenosis, CRF, and CAD were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age (hypertension: 44% in 18–39 years vs 82% in 60–79 years), race (diabetes: Hispanic 49% vs white 30%), and sex (drug abuse: men 3% vs women 1.4%). Using joinpoint regression, prevalence of hypertension increased annually by 1.4%, diabetes by 2%, dyslipidemia by 7%, smoking by 5%, and drug abuse by 7%. Prevalence of CRF, carotid stenosis, and CAD increased annually by 13%, 6%, and 1%, respectively. Proportion of patients with multiple risk factors also increased over time.

Conclusions: Despite numerous guidelines and prevention initiatives, prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in AIS increased across the 2004–2014 period. Proportion of patients with carotid stenosis, CRF, and multiple risk factors also increased. Enhanced risk factor modification strategies and implementation of evidence-based recommendations are needed for optimal stroke prevention.

La proinsulina protegería frente al deterioro cognitivo

Proinsulin protects against age-related cognitive loss through anti-inflammatory convergent pathways

Abstract

Brain inflammaging is increasingly considered as contributing to age-related cognitive loss and neurodegeneration. Despite intensive research in multiple models, no clinically effective pharmacological treatment has been found yet. Here, in the mouse model of brain senescence SAMP8, we tested the effects of proinsulin, a promising neuroprotective agent that was previously proven to be effective in mouse models of retinal neurodegeneration. Proinsulin is the precursor of the hormone insulin but also upholds developmental physiological effects, particularly as a survival factor for neural cells. Adeno-associated viral vectors of serotype 1 bearing the human proinsulin gene were administered intramuscularly to obtain a sustained release of proinsulin into the blood stream, which was able to reach the target area of the hippocampus. SAMP8 mice and the control strain SAMR1 were treated at 1 month of age. At 6 months, behavioral testing exhibited cognitive loss in SAMP8 mice treated with the null vector. Remarkably, the cognitive performance achieved in spatial and recognition tasks by SAMP8 mice treated with proinsulin was similar to that of SAMR1 mice. In the hippocampus, proinsulin induced the activation of neuroprotective pathways and the downstream signaling cascade, leading to the decrease of neuroinflammatory markers. Furthermore, the decrease of astrocyte reactivity was a central effect, as demonstrated in the connectome network of changes induced by proinsulin. Therefore, the neuroprotective effects of human proinsulin unveil a new pharmacological potential therapy in the fight against cognitive loss in the elderly.

La exposición a contaminantes en el camino a la escuela tiene un impacto en el desarrollo cognitivo de los niños

Impact of commuting exposure to traffic-related air pollution on cognitive development in children walking to school☆

Abstract

A few studies have found associations between the exposure to traffic-related air pollution at school and/or home and cognitive development. The impact on cognitive development of the exposure to air pollutants during commuting has not been explored. We aimed to assess the role of the exposure to traffic-related air pollutants during walking commute to school on cognitive development of children. We performed a longitudinal study of children (n = 1,234, aged 7–10 y) from 39 schools in Barcelona (Catalonia, Spain) who commuted by foot to school. Children were tested four times during a 12-month follow-up to characterize their developmental trajectories of working memory (d’ of the three-back numbers test) and inattentiveness (hit reaction time standard error of the Attention Network Test). Average particulate matter ≤2.5 μm (PM2.5), Black Carbon (BC) and NO2 concentrations were estimated using Land Use Regression for the shortest walking route to school. Differences in cognitive growth were evaluated by linear mixed effects models with age-by-pollutant interaction terms. Exposure to PM2.5 and BC from the commutes by foot was associated with a reduction in the growth of working memory (an interquartile range increase in PM2.5 and BC concentrations decreased the annual growth of working memory by 5.4 (95% CI [-10.2, -0.6]) and 4.6 (95% CI [-9.0, -0.1]) points, respectively). The findings for NO2 were not conclusive and none of the pollutants were associated with inattentiveness. Efforts should be made to implement pedestrian school pathways through low traffic streets in order to increase security and minimize children's exposure to air pollutants.

Graphical abstract

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Un defecto epigenético favorece la discapacidad intelectual

Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons

Summary

During development, chromatin-modifying enzymes regulate both the timely establishment of cell-type-specific gene programs and the coordinated repression of alternative cell fates. To dissect the role of one such enzyme, the intellectual-disability-linked lysine demethylase 5C (Kdm5c), in the developing and adult brain, we conducted parallel behavioral, transcriptomic, and epigenomic studies in Kdm5c-null and forebrain-restricted inducible knockout mice. Together, genomic analyses and functional assays demonstrate that Kdm5c plays a critical role as a repressorresponsible for the developmental silencing of germline genes during cellular differentiation and in fine-tuning activity-regulated enhancers during neuronal maturation. Although the importance of these functions declines after birth, Kdm5c retains an important genome surveillance role preventing the incorrect activation of non-neuronal and cryptic promoters in adult neurons.

Graphical Abstract

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Una nueva prueba estimaría el riesgo de enfermedad de Alzheimer con mayor precisión

Polygenic hazard scores in preclinical Alzheimer disease

Abstract

Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ɛ4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high Consortium to Establish a Registry for Alzheimer's Disease (amyloid) and Braak (tau) scores at autopsy, even among APOE ɛ4 noncarriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer neurodegeneration. Ann Neurol 2017;82:484–488

El entorno puede influir en el rendimiento de las personas con trastorno obsesivo compulsivo

Social context modulates cognitive markers in Obsessive-Compulsive Disorder.

ABSTRACT

Error monitoring, cognitive control and motor inhibition control are proposed as cognitive alterations disrupted in obsessive-compulsive disorder (OCD). OCD has also been associated with an increased sensitivity to social evaluations. The effect of a social simulation over electrophysiological indices of cognitive alterations in OCD was examined. A case-control cross-sectional study measuring event-related potentials (ERP) for error monitoring (Error-Related Negativity), cognitive control (N2) and motor control (LRP) was conducted. We analyzed twenty OCD patients and twenty control participants. ERP were recorded during a social game consisting of a visual discrimination task, which was performed in the presence of a simulated superior or an inferior player. Significant social effects (different ERP amplitudes in Superior vs. Inferior player conditions) were found for OCD patients, but not for controls, in all ERP components. Performing the task against a simulated inferior player reduced abnormal ERP responses in OCD to levels observed in controls. The hierarchy-induced ERP effects were accompanied effects over reaction times in OCD patients. Social context modulates signatures of abnormal cognitive functioning in OCD, therefore experiencing a social superiority position impacts over cognitive processes in OCD such as error monitoring mechanisms. These results open the door for the research of new therapeutic choices.

KEYWORDS: Social hierarchy, obsessive-compulsive disorder, evoked potentials, error monitoring process, cognitive control, motor control