Early-life stress diminishes the increase in neurogenesis after exercise in adult female mice.

Exposure to early-life stress (ES) has long-lasting consequences for later cognition and hippocampal plasticity, including adult hippocampal neurogenesis (AHN), i.e., the generation of new neurons from stem/progenitor cells in the adult hippocampal dentate gyrus. We had previously demonstrated a sex-specific vulnerability to ES exposure; female mice exposed to ES from P2-P9 exhibited only very mild cognitive changes and no reductions in AHN as adult, whereas ES-exposed male mice showed impaired cognition closely associated with reductions in AHN. Given the apparent resilience of AHN to ES in females, we here questioned whether ES has also altered the capacity to respond to positive stimuli for neurogenesis. We therefore investigated whether exercise, known for its strong pro-neurogenic effects, can still stimulate AHN in adult female mice that had been earlier exposed to ES. We confirm a strong pro-neurogenic effect of exercise in the dorsal hippocampus of 8-month-old control female mice, but this positive neurogenic response is less apparent in female ES mice. These data provide novel insights in the lasting consequences of ES on hippocampal plasticity in females and also indicate that ES might lastingly reduce the responsiveness of the hippocampal stem cell pool, to exercise, in female mice.

Effects of early-life stress on peripheral and central mitochondria in male mice across ages.

Exposure to early-life stress (ES) increases the vulnerability to develop metabolic diseases as well as cognitive dysfunction, but the specific biological underpinning of the ES-induced programming is unknown. Metabolic and cognitive disorders are often comorbid, suggesting possible converging underlying pathways. Mitochondrial dysfunction is implicated in both metabolic diseases and cognitive dysfunction and chronic stress impairs mitochondrial functioning. However, if and how mitochondria are impacted by ES and whether they are implicated in the ES-induced programming remains to be determined. ES was applied by providing mice with limited nesting and bedding material from postnatal day (P)2-P9, and metabolic parameters, cognitive functions and multiple aspects of mitochondria biology (i.e. mitochondrial electron transport chain (ETC) complex activity, mitochondrial DNA copy number, expression of genes relevant for mitochondrial function, and the antioxidant capacity) were studied in muscle, hypothalamus and hippocampus at P9 and late adulthood (10-12 months of age). We show that ES altered bodyweight (gain), adiposity and glucose levels at P9, but not in late adulthood. At this age, however, ES exposure led to cognitive impairments. ES affected peripheral and central mitochondria in an age-dependent manner. At P9, both muscle and hypothalamic ETC activity were affected by ES, while in hippocampus, ES altered the expression of genes involved in fission and antioxidant defence. In adulthood, alterations in ETC complex activity were observed in the hypothalamus specifically, whereas in muscle and hippocampus ES affected the expression of genes involved in mitophagy and fission, respectively. Our study demonstrates that ES affects peripheral and central mitochondria biology throughout life, thereby uncovering a converging mechanism that might contribute to the ES-induced vulnerability for both metabolic diseases and cognitive dysfunction, which could serve as a novel target for intervention.

Multirater agreement on arthroscopic image quality.

In arthroscopy (minimally invasive orthopaedic surgery), the view is frequently disturbed. To optimize the view, quantification of the arthroscopic image quality is important. Thereto, disturbances were categorized as bleeding, air bubbles, turbidity (synovial fluid), loose fibrous tissue, and attached fibrous tissue, which cover the arthroscopic image area. The goal is to determine the percentages of disturbance coverage for which the view is acceptable. Thirty-two short films of the five disturbances were selected from arthroscopic knee procedures. The films showed disturbances covering different percentages of the image area. Thirty-nine orthopaedic surgeons were asked to judge whether or not the view of each film was acceptable. Multiple-choice questions on irrigation and disturbances were asked. A clear transition from acceptable to unacceptable view was found for bleeding (5 per cent of the covered area was acceptable; 25 per cent was not acceptable), and air bubbles (10 per cent was acceptable; 20 per cent was not acceptable). Loose fibrous tissue showed a gradual transition where 25 per cent was still accepted by a third of the surgeons. Turbidity and attached fibrous tissue were tolerated up to 50 per cent by half of the surgeons. Surgeons using a mechanical pump tolerated a lower percentage of synovial fluid (p<0.05). The most intolerable disturbance was bleeding. The results were consistent and will be used for computerized detection of disturbances.

Zinc protoporphyrin/heme ratio as parameter of iron status in moderately preterm infants: natural course and associations in the first 4 months.

OBJECTIVE: To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants. STUDY DESIGN: ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation. RESULTS: ZnPP/H levels decreased in the first 6 weeks and increased thereafter. At 4 months postnatal age, ZnPP/H was higher in the 11 (8.5%) infants with IDA (mean (s.d.): 260.8 (16.1)) but not in the 27 (21.3%) infants with ID (mean (s.d.): 177.0 (15.1)) compared with normal infants (mean (s.d.): 157.3 (12.5)). CONCLUSION: In moderately preterm infants, ZnPP/H can be of additional value to detect infants at risk for IDA due to iron-deficient erythropoiesis at 4 months of age.

Exposure to chronic early-life stress lastingly alters the adipose tissue, the leptin system and changes the vulnerability to western-style diet later in life in mice.

Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is associated with the ES-induced cognitive impairments. Here, we used an established chronic ES mouse model (from postnatal day (P) 2 to P9) to investigate the short- and long-term effects of ES exposure on parameters of the adipose tissue and the leptin system (i.e. circulating levels and gene expression of leptin and its receptor) in both sexes. Immediately following ES, the offspring exhibited reductions in white adipose tissue (WAT) mass, plasma leptin levels and in leptin mRNA expression in WAT. Furthermore, ES exposure led to increased brown adipose tissue and browning of WAT, which was evident by a drastic increase in uncoupling protein 1 mRNA expression in the inguinal WAT at P9. Notably, the ES-induced reductions in WAT mass, plasma leptin and leptin expression in WAT were sustained into adulthood and were accompanied by changes in body fat distribution, such as a higher ratio between mesenteric WAT and other WATs. Interestingly, while ES exposure increased leptin receptor mRNA expression in the choroid plexus, it was unaltered in the hippocampus. This suggests an adaptation to maintain central leptin homeostasis following ES exposure. In addition, chronic ES exposure resulted in the well-established cognitive impairment in object recognition performance during adulthood, which correlated positively with reductions in WAT mass observed in male, but not in female mice. Finally, to assess if ES leads to a different metabolic phenotype in a moderate obesogenic environment, we measured body fat accumulation of control and ES-exposed mice in response to a moderate western-style diet (WSD) that was provided during adulthood. ES-exposed mice subjected to WSD exhibit a higher increase in adiposity when compared to controls, suggesting that ES exposure might result in a higher vulnerability to develop obesity in a moderate obesogenic environment. To conclude, chronic ES exposure alters parameters of the adipose tissue, leads to central adaptations in leptin regulation and results in higher fat accumulations when exposed to a WSD challenge later in life. A better understanding of these metabolic effects induced by ES might open up new avenues for therapeutic (e.g. nutritional) interventions.

Predictive factors of iron depletion in late preterm infants at the postnatal age of 6 weeks.

BACKGROUND/OBJECTIVES: Late preterm infants (born ⩾32 weeks of gestation) are at risk for developing iron deficiency and iron deficiency anaemia, and this may lead to impaired neurodevelopment. In the Netherlands, there is no guideline for standardised iron supplementation in these infants. Individualised iron supplementation has been suggested (that is, treating those infants with the highest risk), but risk factors for deprived iron stores in this specific group of infants are not well documented. SUBJECTS/METHODS: In this prospective multi-centre study, we analysed the iron status at the postnatal age of 6 weeks of 68 infants born between 32 and 35 weeks of gestation in the Netherlands. Serum ferritin (SF) <70 µg/l in the absence of infection (C-reactive protein <5 mg/l) was defined as iron depletion and whenever in combination with a haemoglobin level <110 mg/dl as iron-depleted anaemia. Medical charts were reviewed to identify risk factors. RESULTS: Iron depletion and iron-depleted anaemia were present in 38.2% and 30.9% of the infants, respectively. Infants with a birth weight <1830 g and a SF <155 µg/l in the first week of life had a 26.4 times higher risk to develop iron depletion (95% confidence interval 3.1-227.0, P=0.003). Multivariate regression analyses also showed that iron depletion was associated with a higher number of blood draws. CONCLUSIONS: Iron depletion is common in late preterm infants at the age of 6 weeks in a setting without standardised iron supplementation. One should consider early individualised iron supplementation for late preterm infants with a low birth weight (<1830 g), and a low SF in the first week of life (<155 µg/l), as they have a high risk to develop iron depletion.

Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age.

BACKGROUND/OBJECTIVES: Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life. SUBJECTS/METHODS: In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation. RESULTS: ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week. CONCLUSIONS: Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.