New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs

Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of the hippocampus and particularly the DG is impaired. For instance, adult neurogenesis is decreased with aging, in both proliferating and differentiation of newborn cells, while in parallel an age-associated decline in cognitive performance is often seen. Surprisingly, the synaptogenic potential of adult-born neurons is only marginally influenced by aging. Therefore, although proliferation, differentiation, and synaptogenesis of adult-born new neurons in the DG are closely related to each other, they are differentially affected by aging. In this review we discuss the crucial roles of a novel class of recently discovered modulators of gene expression, the small non-coding RNAs, in the regulation of adult neurogenesis. Multiple small non-coding RNAs are differentially expressed in the hippocampus. In particular a subgroup of the small non-coding RNAs, the microRNAs, fine-tune the progression of adult neurogenesis. This makes small non-coding RNAs appealing candidates to orchestrate the functional alterations in adult neurogenesis and cognition associated with aging. Finally, we summarize observations that link changes in circulating levels of steroid hormones with alterations in adult neurogenesis, cognitive decline, and vulnerability to psychopathology in advanced age, and discuss a potential interplay between steroid hormone receptors and microRNAs in cognitive decline in aging individuals

Microglial activation arises after aggregation of phosphorylated-tau in a neuron-specific P301S tauopathy mouse model

Alzheimer's disease, progressive supranuclear palsy and frontotemporal dementia are characterized by neuronal expression of aberrant tau protein, tau hyperphosphorylation (pTAU), tau aggregation and neurofibrillary tangle formation sequentially culminating into neuronal cell death, a process termed tauopathy. Our aim was to address at which tauopathy stage neuroinflammation starts and to study the related microglial phenotype. We used Thy1-hTau.P301S (PS) mice expressing human tau with a P301S mutation specifically in neurons. Significant levels of cortical pTAU were present from 2 months onwards. Dystrophic morphological complexity of cortical microglia arose after pTAU accumulation concomitant with increased microglial lysosomal volumes and a significant loss of homeostatic marker Tmem119. Interestingly, we detected increases in neuronal pTAU and postsynaptic structures in the lysosomes of PS microglia. Moreover, the overall cortical postsynaptic density was decreased in 6-month-old PS mice. Together, our results indicate that microglia adopt a pTAU-associated phenotype, and are morphologically and functionally distinct from wild-type microglia after neuronal pTAU accumulation has initiated

Circadian and Ultradian Glucocorticoid Rhythmicity:Implications for the Effects of Glucocorticoids on Neural Stem Cells and Adult Hippocampal Neurogenesis

Total glucocorticoid hormone levels in plasma of various species, including humans, follow a circadian rhythm that is made up from an underlying series of hormone pulses. In blood most of the glucocorticoid is bound to corticosteroid-binding globulin and albumin, resulting in low levels of free hormone. Although only the free fraction is biologically active, surprisingly little is known about the rhythms of free glucocorticoid hormones. We used single-probe microdialysis to measure directly the free corticosterone levels in the blood of freely behaving rats. Free corticosterone in the blood shows a distinct circadian and ultradian rhythm with a pulse frequency of approximately one pulse per hour together with an increase in hormone levels and pulse height toward the active phase of the light/dark cycle. Similar rhythms were also evident in the subcutaneous tissue, demonstrating that free corticosterone rhythms are transferred from the blood into peripheral target tissues. Furthermore, in a dual-probe microdialysis study, we demonstrated that the circadian and ultradian rhythms of free corticosterone in the blood and the subcutaneous tissue were highly synchronized. Moreover, free corticosterone rhythms were also synchronous between the blood and the hippocampus. These data demonstrate for the first time an ultradian rhythm of free corticosterone in the blood that translates into synchronized rhythms of free glucocorticoid hormone in peripheral and central tissues. The maintenance of ultradian rhythms across tissue barriers in both the periphery and the brain has important implications for research into aberrant biological rhythms in disease and for the development of improved protocols for glucocorticoid therapy

Seasonal changes in a sandy beach fish assemblage at Canto Grande, Santa Catarina, South Brazil

Copyright © 2004 Coastal Education and Research Foundation (CERF).Neste trabalho realizaramse amostragens, com uma rede de praia, de modo a estudar a comunidade de peixes de substrato arenoso na enseada de Canto Grande, Santa Catarina, Brasil. As amostragens realizaramse em intervalos de 3 horas durante períodos de 24 h, numa base bimensal, entre Abril de 1996 e Fevereiro de 1997. Verificouse existir uma variação sazonal no número de espécies, densidade de peixes e biomassa, tendo os valores mais elevados ocorrido em Fevereiro (38 espécies, 257.6 peixes 1000 mˉ², 2286.4 g 1000 mˉ²). Recolheuse um total de 67 espécies, pertencentes a 56 géneros e a 33 famílias, sendo a comunidade dominada por sete espécies pertencentes a três famílias: Atherinella brasiliensis (Atherinidae); Brevoortia pectinata, Harengula clupeola e Sardinella brasiliensis (Clupeidae); Anchoviella lepidontostole, Cetengraulis edentulus e Lycengraulis grossidens (Engraulidae). Tanto a diversidade de espécies (H′) como a equitabilidade (J′) foram médias a elevadas ao longo do ano devido à baixa dominância. A maior mudança na estrutura da comunidade ocorreu entre os meses de Inverno (Julho e Agosto) e as outras estações. Nenhuma das espécies dominantes pode ser classificada como residente. Os principais predadores foram Pomatomus saltator (Inverno) e Trichiurus lepturus (Verão). A maior parte das espécies observadas foram ou peixes juvenis ou espécies pelágicas de pequeno tamanho e fortemente gregárias.ABSTRACT: A shallow-water fish assemblage, over a soft, sandy bottom, at Canto Grande, Santa Catarina, Brazil, was sampled with a beach seine. Sampling was undertaken at 3 h intervals over 24 h on a bimonthly basis between April 1996 and February 1997. There was a seasonal variation in the number of species, density of fishes and biomass with the highest values in February (38 species, 257.6 fish 1000 mˉ², 2286.4 g 1000 mˉ²). A total of 67 species, belonging to 56 genera and 33 families were collected and the assemblage was dominated by seven species belonging to three families: Atherinella brasiliensis (Atherinidae); Brevoortia pectinata, Harengula clupeola and Sardinella brasiliensis (Clupeidae); Anchoviella lepidontostole, Cetengraulis edentulus and Lycengraulis grossidens (Engraulidae). Species diversity (H′) and equitability (J′) were medium to high throughout the year due to the low dominance. The largest change in the assemblage structure occurred between winter months (July and August) and the other seasons. None of the dominant species can be classified as a resident. Main predators were Pomatomus saltator (winter) and Trichiurus lepturus (summer). Most of the species observed were either juvenile fish or small pelagic and strongly gregarious species

Navigating competing demands in monitoring and evaluation:Five key paradoxes

Evaluation in complex programs assembling multiple actors and combining various interventions faces contradictory requirements. In this article, we take a management perspective to show how to recognize and accommodate these contradictory elements as paradoxes. Through reflective practice we identify five paradoxes, each consisting of two contradicting logics: the paradox of purpose—between accountability and learning; the paradox of position—between autonomy and involvement; the paradox of permeability—between openness and closedness; the paradox of method—between rigor and flexibility; and the paradox of acceptance—between credibility and feasibility. We infer the paradoxes from our work in monitoring and evaluation and action research embedded in 2SCALE, a program working on inclusive agribusiness and food security in a complex environment. The intractable nature of paradoxes means they cannot be permanently resolved. Making productive use of paradoxes most likely raises new contradictions, which merit a continuous acknowledging and accommodating for well-functioning monitoring and evaluation systems.</p

Monitoring Systemic Change in Inclusive Agribusiness

Evaluations of private sector development programmes look at what changed to the workings of the system, and whether these changes are scalable, resilient, and sustainable. We present an evaluation lens that primarily qualifies changes to the systemic nature of food provisioning in markets. It converts theoretical frameworks into ‘antennae’ receptive to early signs of systemic effects of inclusive agribusiness that fosters food and nutrition security. The tools for this theory-informed approach were developed and applied in 2SCALE, a Dutch-funded programme aiming to incubate inclusive agribusiness and contribute to food and nutrition security goals in Africa. The article reflects on what to monitor to detect early signs of systemic effects and how monitoring can be embedded in unfolding business and partnering processes. It concludes that taking a theory-informed approach gives directionality to strategising and planning, and enhances capacities of partners in inclusive business projects to lead actions towards realising systemic effects

Threat perception abnormalities in children : the role of anxiety disorders symptoms, chronic anxiety, and state anxiety

This study investigated the relative contribution of general (trait) anxiety and state anxiety to threat perception abnormalities in nonreferred children aged 8–13 years (N=299). Children were first asked to complete self-report measures of anxiety disorders symptoms and chronic anxiety. Next, they were individually interviewed using an ambiguous story paradigm from which a number of threat perception indexes were derived. Just before the interview started, children were asked to fill out a measure of state anxiety. Results showed that high levels of general anxiety (as indexed by anxiety disorders symptoms and chronic anxiety) were significantly related to increased threat perception and lower threat thresholds. High levels of state anxiety were also associated with increased threat perception and lower threat thresholds. Regression analyses indicated that general anxiety and state anxiety both accounted for a unique proportion of the variance in threat perception abnormalities, although the contribution of general anxiety was in most cases substantially larger than that of state anxiety. Finally, no support was found for the notion that threat perception abnormalities are the result of the conjoint influence of general anxiety and state anxiety.17 page(s

Glucocorticoid-mediated modulation of morphological changes associated with aging in microglia

Microglia dynamically adapt their morphology and function during increasing age. However, the mechanisms behind these changes are to date poorly understood. Glucocorticoids (GCs) are long known and utilized for their immunomodulatory actions and endogenous GC levels are described to alter with advancing age. We here tested the hypothesis that age-associated elevations in GC levels implicate microglia function and morphology. Our data indicate a decrease in microglial complexity and a concomitant increase in GC levels during aging. Interestingly, enhancing GC levels in young mice enhanced microglial ramifications, while the knockdown of the glucocorticoid receptor expression in old mice aggravated age-associated microglial amoebification. These data suggest that GCs increase ramification of hippocampal microglia and may modulate age-associated changes in microglial morphology

A long-term effect of distal radius fracture on the sensorimotor control of the wrist joint in older adults

Introduction: Sensorimotor control can be disturbed because of pain and trauma. There is scarce comprehension about which component of the sensorimotor system would benefit the most from treatment in distal radius fracture (DRF). Purpose of the Study: The purpose of this study was to determine whether the sensorimotor control of subjects with a history of DRF impaired compared with healthy subjects. If so, which component of the sensorimotor system is most affected. Methods: Nine healthy participants and 11 participants with a DRF history executed posture and reproduction tasks in interaction with a robotic wrist manipulator. A posture task with force perturbations assess sensorimotor control. Position and force reproduction tasks assessed sensory feedback. Electromyography recorded the muscle activity to study the motor part of the sensorimotor system. Study Design: Cross-sectional case-control. Results: The results showed that the motor responses to the perturbations during the posture task did not differ significantly, whereas the position reproduction did significantly differ between the 2 groups. Moreover, participants with a DRF history did not adapt to the changed dynamics of the environment during the posture task, whereas the controls did. Discussion: The results of this study imply that processing of sensory position feedback is impaired in people with a DRF history while sensorimotor control during a posture task is unaffected. A possible explanation for these results is that different neural networks are involved during reproduction and posture tasks. Conclusions: A history of DRF is related to disturbed processing of sensory feedback of the sensorimotor system, especially the Joint Position Sense, which leads to an impairment in detecting a changed environment and adapting to it. Impaired Joint Position Sense and thereby the inability to adapt adequately to a changing environment should be taken into account during the rehabilitation of patients with DRF.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Biomechatronics & Human-Machine Contro