MicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of ∼22 nucleotides that regulate gene expression at the level of translation and play vital roles in hippocampal neuron development, function and plasticity. Here, we performed a systematic and in-depth analysis of miRNA expression profiles in cultured hippocampal neurons during development and after induction of neuronal activity. MiRNA profiling of primary hippocampal cultures was carried out using locked nucleic-acid-based miRNA arrays. The expression of 264 different miRNAs was tested in young neurons, at various developmental stages (stage 2–4) and in mature fully differentiated neurons (stage 5) following the induction of neuronal activity using chemical stimulation protocols. We identified 210 miRNAs in mature hippocampal neurons; the expression of most neuronal miRNAs is low at early stages of development and steadily increases during neuronal differentiation. We found a specific subset of 14 miRNAs with reduced expression at stage 3 and showed that sustained expression of these miRNAs stimulates axonal outgrowth. Expression profiling following induction of neuronal activity demonstrates that 51 miRNAs, including miR-134, miR-146, miR-181, miR-185, miR-191 and miR-200a show altered patterns of expression after NMDA receptor-dependent plasticity, and 31 miRNAs, including miR-107, miR-134, miR-470 and miR-546 were upregulated by homeostatic plasticity protocols. Our results indicate that specific miRNA expression profiles correlate with changes in neuronal development and neuronal activity. Identification and characterization of miRNA targets may further elucidate translational control mechanisms involved in hippocampal development, differentiation and activity-depended processes.

We confirm that not only underweight but also obesity is associated with physical frailty. Obesity also seems to be associated with cognitive frailty. Further, frailty prevention should focus on multiple domains and target individuals at a younger age (<65yrs).

BackgroundAccumulation of problems in physical, psychological, cognitive, or social functioning is characteristic for frail individuals. Using a four-domain approach of frailty, this study explored how sociodemographic and lifestyle factors, life events and health are associated with frailty.MethodsThe study sample included 4019 men and women (aged 40–81 years) examined during the fifth round (2008–2012) of the Doetinchem Cohort Study. Four domains of frailty were considered: physical (≥4 of 8 criteria: unintentional weight loss, exhaustion, strength, perceived health, walking, balance, hearing and vision impairments), psychological (2 criteria: depressive symptoms, mental health), cognitive (<10th percentile on global cognitive functioning), and social frailty (≥2 of 3 criteria: loneliness, social support, social participation). Logistic regression was used to study the cross-sectional association of sociodemographic factors, lifestyle, life events and chronic diseases with frailty domains.ResultsAbout 17% of the population was frail on one or more domains. Overlap between the frailty domains was limited since 82% of the frail population was frail on one domain only. Low educated respondents were at higher risk of being psychologically and socially frail. Having multiple diseases was associated with a higher risk of being physically and psychologically frail. Being physically active was consistently associated with a lower risk of frailty on each of the four domains. Short or long sleep duration was associated with a higher risk of being physically, psychologically, and socially frail.ConclusionsSociodemographic factors, lifestyle and multimorbidity contributed differently to the four frailty domains. It is important to consider multiple frailty domains since this helps to identify different groups of frail people, and as such to provide tailored care and support. Lifestyle factors including physical activity, smoking and sleep duration were associated with multiple domains of frailty.Electronic supplementary materialThe online version of this article doi: 10.1186/s12877-017-0595-0) contains supplementary material, which is available to authorized users.

Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i.e. biomarkers and markers, for the physical, cognitive, and psychological frailty domains. We used univariate (Rank-ANOVA) and multivariate (elastic net) approaches on the RASIG study population (age range: 35-74 years, n = 2220) of the MARK-AGE study to study up to 331 (bio)markers between individuals with and without frailty for each domain. Biomarkers and markers identified by both approaches were studied further regarding their association with frailty using logistic regression. Univariately, we found lower levels of antioxidants, including β-cryptoxanthin and zeaxanthin, in those who were physically, cognitively or psychologically frail. Additionally, self-reported health was worse in these three frail groups. Multivariately, we observed lower levels of β-cryptoxanthin and zeaxanthin in the cognitively frail. Levels of these carotenoids were inversely associated with the risk of being cognitively frail after adjusting for confounders. Antioxidants and self-reported health are potential (bio)markers to detect persons at risk of becoming frail. The biomarkers identified may indicate the involvement of inflammation in frailty, especially for physical and cognitive frailty.