Hippocampal IGF-1 expression, neurogenesis and slowed aging: clues to longevity from mutant mice

Recent studies point out the important role of IGF and insulin-related signaling pathways in the control of longevity of laboratory animals. The Ames dwarf mouse is a murine model of circulating GH and IGF-1 deficiency that exhibits dwarf phenotype characteristics and significantly extends lifespan. It is interesting to know that Ames dwarf mice do not experience an age-related decline in cognitive function when compared to their young counterparts. In this study, the most recent works on local GH and IGF-1 expression in the hippocampus of Ames mice are briefly reviewed

Retinoic Acid Restores Adult Hippocampal Neurogenesis and Reverses Spatial Memory Deficit in Vitamin A Deprived Rats

A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD) on neurogenesis and memory and the ability of retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function

The direct healthcare costs associated with psychological distress and major depression : A population-based cohort study in Ontario, Canada

The objective of our study was to estimate direct healthcare costs incurred by a population-based sample of people with psychological distress or depression. We used the 2002 Canadian Community Health Survey on Mental Health and Well Being and categorized individuals as having psychological distress using the Kessler-6, major depressive disorder (MDD) using DSM-IV criteria and a comparison group of participants without MDD or psychological distress. Costs in 2013 USD were estimated by linking individuals to health administrative databases and following them until March 31, 2013. Our sample consisted of 9,965 individuals, of whom 651 and 409 had psychological distress and MDD, respectively. Although the age-and-sex adjusted per-capita costs were similarly high among the psychologically distressed ($3,364, 95$2,791, $3,937) and those with MDD ($3,210, 95% CI: $2,413,$4,008) compared to the comparison group ($2,629, 95$2,312, $2,945), the population-wide excess costs for psychological distress ($441 million) were more than twice that for MDD ($210 million) as there was a greater number of people with psychological distress than depression. We found substantial healthcare costs associated with psychological distress and depression, suggesting that psychological distress and MDD have a high cost burden and there may be public health intervention opportunities to relieve distress. Further research examining how individuals with these conditions use the healthcare system may provide insight into the allocation of limited healthcare resources while maintaining high quality care

Role of C/EBPβ Transcription Factor in Adult Hippocampal Neurogenesis

[Background]: The dentate gyrus of the hippocampus is one of the regions in which neurogenesis takes place in the adult brain. We have previously demonstrated that CCAAT/enhancer binding protein β (C/EBPβ) is expressed in the granular layer of the dentate gyrus of the adult mouse hippocampus. Taking into account the important role of C/EBPβ in the consolidation of long term memory, the fact that newborn neurons in the hippocampus contribute to learning and memory processes, and the role of this transcription factor, previously demonstrated by our group, in regulating neuronal differentiation, we speculated that this transcription factor could regulate stem/progenitor cells in this region of the brain. [Methodologu/Principal Findings]: Here, we show, using C/EBPβ knockout mice, that C/EBPβ expression is observed in the subset of newborn cells that proliferate in the hippocampus of the adult brain. Mice lacking C/EBPβ present reduced survival of newborn cells in the hippocampus, a decrease in the number of these cells that differentiate into neurons and a diminished number of cells that are proliferating in the subgranular zone of the dentate gyrus. These results were further confirmed in vitro. Neurosphere cultures from adult mice deficient in C/EBPβ present less proliferation and neuronal differentiation than neurospheres derived from wild type mice. [Conclusions/Significance]: In summary, using in vivo and in vitro strategies, we have identified C/EBPβ as a key player in the proliferation and survival of the new neurons produced in the adult mouse hippocampus. Our results support a novel role of C/EBPβ in the processes of adult hippocampal neurogenesis, providing new insights into the mechanisms that control neurogenesis in this region of the brain.This work was supported by a postdoctoral fellowship of the Consejo Superior de Investigaciones Cientificas (M.C.-C.) Grant Sponsor: Ministerio de Investigación y Ciencia; Grant numbers: SAF2007-62811 and SAF2010-16365. CIBERNED is funded by the Instituto de Salud Carlos III.Peer reviewe

The relationship between various measures of obesity and arterial stiffness in morbidly obese patients

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with increased risk of cardiovascular disease. Arterial stiffness assessed by carotid femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of body composition affect arterial stiffness.</p> <p>Methods</p> <p>This is an analysis of cross-sectional baseline data from a controlled clinical trial addressing changes in arterial stiffness after either surgery or lifestyle intervention in a population of morbidly obese patients. High-fidelity applanation tonometry (Millar^®, Sphygmocor^®) was used to measure pulse wave velocity (PWV). Carotid femoral PWV is a direct measure of arterial stiffness and is considered to be the gold standard method. The Inbody 720 Body Composition Analyzer was used for bioelectrical impedance analysis (BIA). Spearman's correlation, independent samples <it>t</it>-test, chi-square tests, Fisher's exact test and multiple linear regression analyses were used as statistical methods.</p> <p>Results</p> <p>A total of 133 patients (79 women), with a mean (SD) age of 43 (11) years were included in the study. Men had a significantly higher prevalence of obesity related comorbidities and significantly higher PWV, 9.1 (2.0) m/s vs. 8.1 (1.8) m/s, p = 0.003, than women. In the female group, PWV was positively correlated with WC, WHtR, BMI and visceral fat area. In the male group, PWV was negatively correlated with BMI. Multiple linear regression analysis showed that increasing BMI, WC, WHtR, visceral fat area and fat mass were independently associated with higher PWV in women, but not in men, after adjustment for age, hypertension and type 2 diabetes.</p> <p>Conclusion</p> <p>Most measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT00626964">NCT00626964</a></p

Tracking Subtle Stereotypes of Children with Trisomy 21: From Facial-Feature-Based to Implicit Stereotyping

Background: Stigmatization is one of the greatest obstacles to the successful integration of people with Trisomy 21 (T21 or Down syndrome), the most frequent genetic disorder associated with intellectual disability. Research on attitudes and stereotypes toward these people still focuses on explicit measures subjected to social-desirability biases, and neglects how variability in facial stigmata influences attitudes and stereotyping. Methodology/Principal Findings: The participants were 165 adults including 55 young adult students, 55 non-student adults, and 55 professional caregivers working with intellectually disabled persons. They were faced with implicit association tests (IAT), a well-known technique whereby response latency is used to capture the relative strength with which some groups of people—here photographed faces of typically developing children and children with T21—are automatically (without conscious awareness) associated with positive versus negative attributes in memory. Each participant also rated the same photographed faces (consciously accessible evaluations). We provide the first evidence that the positive bias typically found in explicit judgments of children with T21 is smaller for those whose facial features are highly characteristic of this disorder, compared to their counterparts with less distinctive features and to typically developing children. We also show that this bias can coexist with negative evaluations at the implicit level (with large effect sizes), even among professional caregivers

Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

IMPORTANCE: A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age. OBJECTIVE: To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets. DESIGN, SETTING, AND PARTICIPANTS: This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study. MAIN OUTCOMES AND MEASURES: We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age. RESULTS: We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers

Chapter 20 - Acinetobacter Infections

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