The impact of early-life conditions on visual discrimination abilities in free-ranging laying hens.

Conditions during incubation and rearing can greatly affect the developmental trajectory of chickens, in a positive and negative way. In this study, the effect of early-life conditions on the visual discrimination abilities of adult, free-ranging laying hens was examined. These early-life treatments entailed incubation in a 12/12h green light/dark cycle and rearing with Black soldier fly larvae (BSFL) as foraging enrichment. Through a modified pebble-floor test, 171 hens of 41 to 42 wk old, housed in mobile stables with outdoor access, were tested for their ability to discriminate between food and nonfood items (mealworms and decoy mealworms). Each hen was allowed 60 pecks during the trial, from which the overall success rate, as well as within-trial learning was investigated. The latter was accomplished by dividing the 60 pecks into 3 blocks of 20 pecks and comparing the success rate between these blocks. Due to another ongoing experiment on range use, roughly half the hens received range enrichment (mealworms) at the time of testing, so this was included as a covariate in the analysis. Incubation with green light did not have an effect on the visual discrimination abilities of adult laying hens. Rearing with BSFL did have a limited beneficial effect on the visual discrimination abilities, as evidenced by a higher success rate during the first block of the visual discrimination trial. These enhanced visual discrimination abilities might be useful in a more complex free-range setting, where the animals have more foraging opportunities. Hens that received range enrichment at the time of testing, also had a higher success rate during the visual discrimination test, though they had a lower degree of test completion, likely due to habituation to the mealworms as an enrichment. The positive effects of BSFL during rearing and mealworms during the laying period stress the importance of enrichment throughout the life of the hens.

Analysis of hippocampal synaptic function in a rodent model of early life stress.

Background: Early life stress (ELS) is an important risk factor in the aetiology of depression. Developmental glucocorticoid exposure impacts multiple brain regions with the hippocampus being particularly vulnerable. Hippocampal mediated behaviours are dependent upon the ability of neurones to undergo long-term potentiation (LTP), an N-methyl-D-aspartate receptor (NMDAR) mediated process. In this study we investigated the effect of ELS upon hippocampal NMDAR function. Methods: Hooded Long-Evans rat pups (n=82) were either undisturbed or maternally separated for 180 minutes per day (MS180) between post-natal day (PND) 1 and PND14. Model validation consisted of sucrose preference (n=18) and novelty supressed feeding (NSFT, n=34) tests alongside assessment of corticosterone (CORT) and paraventricular nucleus (PVN) cFos reactivity to stress and hippocampal neurogenesis (all n=18). AMPA/NMDA ratios (n=19), miniEPSC currents (n=19) and LTP (n=15) were assessed in whole-cell patch clamp experiments in CA1 pyramidal neurones. Results: MS180 animals showed increased feeding latency in the NSFT alongside increased overall CORT in the restraint stress experiment and increased PVN cFos expression in males but no changes in neurogenesis or sucrose preference. MS180 was associated with a lower AMPA/NMDA ratio with no change in miniEPSC amplitude or area. There was no difference in short- or long-term potentiation between MS180 and control animals nor were there any changes during the induction protocol. Conclusions: The MS180 model showed a behavioural phenotype consistent with previous work. MS180 animals showed increased NMDAR function with preliminary evidence suggesting that this was not concurrent with an increase in LTP.

Highly stressful early life events are the biggest risk factor for developing depression in adulthood. The hippocampus is a brain region that is highly susceptible to this stress and is crucial for coordinating learning and memory which underpins many aspects of cognitive function. Our study investigated if changes in the way that the neurons in the hippocampus communicate could provide explanations as to why early life stress predisposes to depression. We used an animal model of early life stress where rat pups are separated from their mother for three hours per day during their early life. Upon adulthood this resulted in the rats being slower to eat food in a new environment, a standard test of anxiety behaviour. We then used a technique called ex-vivo patch clamp electrophysiology to study how the individual neurons in their hippocampi and their connections functioned after early life stress. We measured the relative power of the signals from two key synaptic receptors essential for communication between neurons: AMPA and NMDA receptors. AMPA receptors are the key receptors enabling communication between neurons at synapses whereas NMDA receptors allow a neuron to become more sensitive to input signals and adapt synaptic strength. Animals with early life stress had more NMDA receptor function relative to AMPA function compared to control animals. We used a technique called miniEPSC recordings to rule out any change in AMPA receptor function in ELS animals meaning an effect specific to NMDA receptors. However, we found no changes to the ability for synapses to adapt their strength between groups. This work presents evidence for changes in hippocampal neurons and synapses caused by early life stress but further work is needed to understand how this relates to depression.

Impact of maternal protein restriction on the proteomic landscape of male rat lungs across the lifespan.

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.

Early life exposures of childhood asthma and allergies-an epidemiologic perspective.

Children around the world are continuing to develop and suffer from chronic lung diseases such as asthma. Childhood asthma commonly presents with recurrent episodes of cough, shortness of breath, and wheezing, all of which can lead to missed school days and hospitalization admissions. The role of environmental pollutants and aeroallergens has been increasingly recognized in relation to asthma etiology. We showcase the impacts of air pollution and pollen exposures in early life on childhood asthma and allergies through an epidemiologic perspective. We also examine the effects of indoor microbial exposures such as endotoxin and glucan on allergic diseases in schoolchildren as many spend most of their time in a household or classroom setting. Findings of this work can assist in the identification of key environmental factors in critical life periods and improve clinicians' diagnoses of asthma during early childhood.

The early life exposome and autism risk: a role for the maternal microbiome?

Autism spectrum disorders (ASD) are highly heritable, heterogeneous neurodevelopmental disorders characterized by clinical presentation of atypical social, communicative, and repetitive behaviors. Over the past 25 years, hundreds of ASD risk genes have been identified. Many converge on key molecular pathways, from translational control to those regulating synaptic structure and function. Despite these advances, therapeutic approaches remain elusive. Emerging data unearthing the relationship between genetics, microbes, and immunity in ASD suggest an integrative physiology approach could be paramount to delivering therapeutic breakthroughs. Indeed, the advent of large-scale multi-OMIC data acquisition, analysis, and interpretation is yielding an increasingly mechanistic understanding of ASD and underlying risk factors, revealing how genetic susceptibility interacts with microbial genetics, metabolism, epigenetic (re)programming, and immunity to influence neurodevelopment and behavioral outcomes. It is now possible to foresee exciting advancements in the treatment of some forms of ASD that could markedly improve quality of life and productivity for autistic individuals. Here, we highlight recent work revealing how gene X maternal exposome interactions influence risk for ASD, with emphasis on the intrauterine environment and fetal neurodevelopment, host-microbe interactions, and the evolving therapeutic landscape for ASD.

Antrodia camphorata Supplementation during Early Life Alters Gut Microbiota and Inhibits Young-Onset Intestinal Tumorigenesis in APC1638N Mice Later in Life.

Young-onset colorectal cancer is an increasing concern worldwide due to the growing prevalence of Westernized lifestyles in childhood and adolescence. Environmental factors during early life, particularly early-life nutrition, significantly contribute to the increasing incidence. Recently, there have been reports of beneficial effects, including anti-inflammation and anti-cancer, of a unique fungus (Antrodia camphorate, AC) native to Taiwan. The objective of this study is to investigate the impact of AC supplementation in early life on the development of young-onset intestinal tumorigenesis. APC1638N mice were fed with a high-fat diet (HF) at 4-12 weeks of age, which is equivalent to human childhood/adolescence, before switching to a normal maintenance diet for an additional 12 weeks up to 24 weeks of age, which is equivalent to young to middle adulthood in humans. Our results showed that the body weight in the HF groups significantly increased after 8 weeks of feeding (p < 0.05). Following a switch to a normal maintenance diet, the change in body weight persisted. AC supplementation significantly suppressed tumor incidence and multiplicity in females (p < 0.05) and reduced IGF-1 and Wnt/ß-catenin signaling (p < 0.05). Moreover, it altered the gut microbiota, suppressed inflammatory responses, and created a microenvironment towards suppressing tumorigenesis later in life.

Cumulative adversity and survival in the wild.

Protecting populations contending with co-occurring stressors requires a better understanding of how multiple early-life stressors affect the fitness of natural systems. However, the complexity of such research has limited its advancement and prevented us from answering new questions. In human studies, cumulative risk models predict adult health risk based on early adversity exposure. We apply a similar framework in wild yellow-bellied marmots (Marmota flaviventer). We tested cumulative adversity indices (CAIs) across different adversity types and time windows. All CAIs were associated with decreased pup survival and were well supported. Moderate and acute, but not standardized CAIs were associated with decreased lifespan, supporting the cumulative stress hypothesis and the endurance of early adversity. Multivariate models showed that differences in lifespan were driven by weaning date, precipitation, and maternal loss, but they performed poorly compared with CAI models. We highlight the development, utility, and insights of CAI approaches for ecology and conservation.

Gut Microbiome in Children with Congenital Heart Disease After Cardiopulmonary Bypass Surgery (GuMiBear Study).

The gut microbiome of infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery (CPB) is at risk of profound alteration. The aim of this study was to examine the gut microbiome pre- and post-bypass surgery to explore potential implications of altered gut biodiversity. A prospective cohort study involving infants with CHD who underwent CPB was performed. Faecal samples were collected from infants alongside the collection of demographic and clinical data in order to examine gut microbiome changes before and after surgery. 16S rRNA sequencing analysis was performed on DNA isolated from stool samples to determine changes in gut microbiome composition. Thirty-three patients were recruited, with samples from thirteen of these available for final analysis. Compared with healthy, matched controls, at a genus level, pre-operative samples for infants with CHD demonstrated a higher relative abundance of Escherichia-Shigella (31% vs 2-6%) and a lower relative abundance of Bifidobacterium (13% vs 40-60%). In post-operative samples, the relative abundance of Escherichia-Shigella (35%), Enterococcus (11%), Akkermansia (6%), and Staphylococcus (5%) were higher than pre-op samples. One infant developed post-operative necrotising-enterocolitis (NEC). They displayed a marked abundance of the Enterococcus (93%) genus pre-operatively. This study demonstrates that infants with CHD have an altered gut microbiome when compared with healthy controls and there might be a possible link between an abundance of virulent species and NEC.

Defining and distinguishing early life stress, trauma, adversity, toxic and chronic stress and allostatic load: a descriptive review.

AIMS: Various concepts are used to study the impact of stress on childhood development. These concepts are often used inconsistently or interchangeably. Our main objectives were to determine how selected stress concepts (chronic stress, toxic stress, allostatic load, early life stress, childhood adversity, childhood trauma and adverse childhood experiences; ACEs) are defined, operationalized and described, and to provide a theoretical context to aid the choice for a preferred concept in public health research. METHODS: For this descriptive review, we systematically searched for literature published before 4 August 2021, on PubMed, Embase and PsycInfo. Two independent reviewers included studies. Exclusion criteria were: no systematic review, not peer reviewed, not published in English, selected stress concepts were no predetermined variable or a substantial topic in the discussion, full text was unobtainable or study described non-human or non-childhood populations. Data extraction forms were used. Descriptives were gathered, publication fields were identified through Journal Citation Reports categories, and verbatim descriptions were ordered in text and Venn diagrams. RESULTS: Of 264 screened studies, 124 were included. ACEs, childhood adversity and childhood trauma were used most. ACEs were the main concept used most frequently (47.6%). A total of 11 of 14 public and environmental health journals used ACEs. All concepts refer to prolonged, repeated, interpersonal stress from 0 to 18 years, that can alter physiological systems. Four concepts were stressor oriented, two concepts focused on stress response and effect and one on the state of challenged homeostasis. CONCLUSIONS: ACEs seem most fitting for public health setting, due to their operationalizability, large set of core experiences and widespread use.

Development of systemic and mucosal immune responses against gut microbiota in early life and implications for the onset of allergies.

The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants' first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.

Communications, engagement, and dissemination strategies for the HEALthy Brain and Child Development (HBCD) Study.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Study success depends on the engagement and inclusion of diverse populations of pregnant participants and their children across the United States, including those at high and low risk for prenatal substance use. The Communications, Engagement, and Dissemination (CED) Committee is responsible for the development and implementation of a strategy to promote awareness about the study, encourage participation, and engage HBCD families, community partners, and collaborators. Initial work involved developing versatile recruitment and awareness materials with a consistent and inclusive message that reduces stigma and negative bias towards marginalized populations, including people with substance use and other mental health conditions. These efforts were shaped by an integrated product development workflow and early engagement with HBCD partners to address challenges. Ongoing work includes the expansion of HBCD outreach through newsletters and social media platforms with an emphasis on protecting participant privacy. Future activities will focus on disseminating scientific information through generation of infographics and webinars that will inform participants, families, and the public of discoveries generated from HBCD Study data.

Bilirubin metabolism in early life and respiratory health during preschool age: A combined analysis of two independent birth cohorts.

BACKGROUND: Bilirubin has antioxidant properties, and elevated levels within the normal range have been associated with improved lung function and decreased risk of asthma in adults, but studies of young children are scarce. Here, we investigate associations between bilirubin in early life and respiratory health endpoints during preschool age in two independent birth cohorts. METHODS: Bilirubin metabolites were assessed at ages 0.5, 1.5, and 6 years in COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) and ages 1, 3, and 6 years in the VDAART (The Vitamin D Antenatal Asthma Reduction Trial) cohort. Meta-analyses were done to summarize the relationship between levels of bilirubin metabolites and asthma, infections, lung function, and allergic sensitization until age 6 across the cohorts. Interaction with the glucuronosyltransferase family 1 member A1 (UGT1A) genotype encoding for an enzyme in the bilirubin metabolism was explored, and metabolomics data were integrated to study underlying mechanisms. FINDINGS: Increasing bilirubin (Z,Z) at ages 1.5-3 years was associated with an increased risk of allergic sensitization (adjusted relative risk [aRR] = 1.85 [1.20-2.85], p = 0.005), and age 6 bilirubin (Z,Z) also showed a trend of association with allergic sensitization at age 6 (aRR = 1.31 [0.97-1.77], p = 0.08), which showed significant interaction for the age 6 bilirubin (Z,Z)xUGT1A genotype. Further, increasing bilirubin (E,E), bilirubin (Z,Z), and biliverdin at ages 1.5-3 years was associated with a lower forced expiratory volume at age 6 (aRR range = 0.81-0.91, p < 0.049) but without a significant interaction with the UGT1A genotype (p interactions > 0.05). Network analysis showed a significant correlation between bilirubin metabolism and acyl carnitines. There were no associations between bilirubin metabolites and the risk of asthma and infections. CONCLUSIONS: Bilirubin metabolism in early life may play a role in childhood respiratory health, particularly in children with specific UGT1A genotypes. FUNDING: The Lundbeck Foundation (Grant no R16-A1694), The Ministry of Health (Grant no 903516), Danish Council for Strategic Research (Grant no 0603-00280B), and The Capital Region Research Foundation have provided core support to the COPSAC research center. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 946228). The Vitamin D Antenatal Asthma Reduction Trial (VDDART, ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI, U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS). Metabolomics work by VDAART was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL123915 and R01HL141826. S.T.W. was supported by R01HL091528 from the NHLBI, UG3OD023268 from Office of The Director, National Institute of Health, and P01HL132825 from the NHLBI.

Late maternal separation provides resilience to chronic variable stress-induced anxiety- and depressive-like behaviours in male but not female mice.

Maternal separation can have long-lasting effects on an individual's susceptibility to stress later in life. Maternal separation during the postnatal period is a commonly used paradigm in rodents to investigate the effects of early life stress on neurobehavioural changes and stress responsiveness. However, maternal separation during stress hyporesponsive and responsive periods of postnatal development may differ in its effects on stress resilience. Therefore, we hypothesised that late maternal separation (LMS) from postnatal day 10 to 21 in mice may have different effect on resilience than early maternal separation during the first week of postnatal life. Our results suggested that male LMS mice are more resilient to chronic variable stress (CVS)-induced anxiety and depressive-like behaviour as confirmed by the open field, light-dark field, elevated plus maze, sucrose preference and tail suspension tests. In contrast, female LMS mice were equally resilient as non-LMS female mice. We found increased expression of NPY, NPY1R, NPY2R, NPFFR1, and NPFFR2 in the hypothalamus of male LMS mice whereas the opposite effect was observed in the hippocampus. LMS in male and female mice did not affect circulating corticosterone levels in response to psychological or physiological stressors. Thus, LMS renders male mice resilient to CVS-induced neurobehavioural disorders in adulthood.

Sexual dimorphism exists in the effects of late maternal separation (LMS)LMS provides resilience to stress-induced anxiety and depression in male miceLMS upregulates NPY and NPVF system in the hypothalamus of male miceNo effect of LMS on stress-induced corticosterone levels.

Exploring the impact of maternal early life adversity on interoceptive sensibility in pregnancy: implications for prenatal depression.

PURPOSE: Pregnancy is a sensitive period of development in adult life characterized by massive changes in physical, emotional, and cognitive function. Such changes may be adaptive, e.g., facilitating adjustment to physical demands, but they may also reflect or contribute to risks inherent to this stage of life, e.g., prenatal depression. One cognitive ability that may undergo change during pregnancy and contribute to mental wellness is interoception - the ability to perceive, integrate, and model sensory information originating from the body. Strong interoceptive abilities are associated with lower rates of depression in non-pregnant adult populations, and interoception is generally weaker in individuals at higher risk for depression, for example, exposure to early life adversity (ELA). In the present online, cross-sectional study, we investigated whether interoception in pregnant women differed based on histories of ELA, in ways that increased their relative risk for prenatal depression symptoms. METHODS: The pregnant individuals were in the second trimester of their first pregnancy and were compared to a group of nulliparous, non-parenting women. RESULTS: Previous exposure to ELA significantly moderated pregnancy-related differences in self-reported interoception (interoceptive sensibility). A further moderated-mediation analysis revealed that the extent to which interoceptive sensibility buffered against depressive symptoms was conditional on ELA exposure, suggesting more ELA is associated with lower interoceptive sensibility during pregnancy, which increased prenatal depression risk. CONCLUSIONS: Together this work suggests that levels of interoception during pregnancy are sensitive to previous adversity exposure. It also suggests that interoceptive-focused interventions for preventing/treating prenatal depressive symptoms in high-risk women may be worth exploring.

Social, not genetic, programming of development and stress physiology of a colonial seabird.

Phenotypic differences often stem from genetic/maternal differences and/or early-life adaptations to local environmental conditions. In colonial animals, little is known on how variation in the social environment is embedded into individual phenotypes, nor what the consequences are on individual fitness. We conducted an experimental cross-fostering study on king penguins (Aptenodytes patagonicus), exchanging eggs among 134 pairs breeding in high-density (67 pairs) or low-density (67 pairs) areas of the same breeding colony. We investigated differences in parent and chick phenotypes and survival in relation to the density of their origin and foster environment. Adults breeding in colony areas of high density exhibited decreased resting behaviour and increased aggression and vigilance, increased hypometabolism during incubation fasts, and more moderate corticosterone responses shaped by exposure to chronic stressors (e.g. constant aggression by neighbours). Chick phenotypes were more influenced by the environment in which they were raised than their genetic/maternal origin. Chicks raised in high-density colonial environments showed enhanced weight gain and survival rates regardless of the density of their genetic parents' breeding areas. Our study experimentally shows advantages to breeding in colonial areas of higher breeder densities in king penguins, and highlights the importance of social settings in shaping phenotype expression in colonial seabirds.

Effect of enhanced plane of nutrition in early life on the transcriptome and proteome of the anterior pituitary gland in Angus heifer calves.

BACKGROUND: Enhanced nutrition during the early calfhood period has been shown to lead to earlier pubertal development in heifer calves. This is of interest as earlier pubertal onset can subsequently facilitate earlier calving which can economically benefit production systems. Reproductive development in heifers is regulated by the hypothalamic-pituitary-ovarian signalling pathway. In particular the anterior pituitary gland is central to reproductive development, through the dynamics of gonadotropic pulsatility. However, despite clear knowledge of the influence of enhanced dietary intake on subsequent reproductive development, the molecular control governing this response in the pituitary gland within the hypothalamic-pituitary-ovarian signalling axis in heifer calves is not fully understood. The objective of this study was to examine the effect of an enhanced plane of nutrition during early life on the anterior pituitary gland of heifer calves through both transcriptomic and proteomic analyses. Between 3 and 21 weeks of age, heifer calves were offered either a high (HI, n = 14) or moderate (MOD, n = 14) plane of nutrition, designed to elicit target growth rates of 1.2 and 0.5 kg/d for HI and MOD groups, respectively. All calves were euthanised at 21 weeks of age and anterior pituitary tissue harvested for subsequent use in global transcriptomic and proteomic analyses. RESULTS: Average daily gain was affected by diet (P < 0.001) and was 1.18 and 0.50 kg/day, for HI and MOD calves, respectively. RNAseq analysis resulted in the identification of 195 differentially expressed genes (Padj<0.05; fold change > 1.5), with 277 proteins identified as differentially abundant (Padj<0.05; fold change > 1.5) between contrasting dietary treatment groups. Biochemical pathway analysis of differentially affected genes and proteins revealed an enrichment for both growth hormone and GnRH signalling pathways (Padj.<0.05). Additionally, pathway analysis predicted an effect of enhanced dietary intake on endocrine function within the anterior pituitary gland as well as on reproductive system development and function (Padj.<0.05). CONCLUSIONS: Results from this study show that an enhanced dietary intake during early calfhood affected the molecular control of the anterior pituitary gland in heifer calves in early life.

Patterns of spawning and settlement of reef fishes as strategic responses to post-settlement competition.

Settlement is a critical transition in the life history of reef fish, and the timing of this event can have a strong effect on fitness. Key factors that influence settlement timing are predictable lunar cyclic variation in tidal currents, moonlight, and nocturnal predation risk as larvae transition from pelagic to benthic environments. However, populations typically display wide variation in the arrival of settlers over the lunar cycle. This variation is often hypothesized to result from unpredictable conditions in the pelagic environment and bet-hedging by spawning adults. Here, we consider the hypothesis that the timing of spawning and settlement is a strategic response to post-settlement competition. We use a game theoretic model to predict spawning and settlement distributions when fish face a tradeoff between minimizing density-independent predation risk while crossing the reef crest vs. avoiding high competitor density on settlement habitat. In general, we expect competition to spread spawning over time such that settlement is distributed around the lunar phase with the lowest predation risk, similar to an ideal free distribution in which competition spreads competitors across space. We examine the effects of overcompensating density dependence, age-dependent competition, and competition among daily settler cohorts. Our model predicts that even in the absence of stochastic variation in the larval environment, competition can result in qualitative divergence between spawning and settlement distributions. Furthermore, we show that if competitive strength increases with settler age, competition results in covariation between settler age and settlement date, with older larvae settling when predation risk is minimal. We predict that competition between daily cohorts delays peak settlement, with priority effects potentially selecting for a multimodal settlement distribution.

Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity.

Abnormal development and function of the hippocampus are two of the most consistent findings in humans and rodents exposed to early-life adversity (ELA), with males often being more affected than females. Using the limited bedding (LB) paradigm as a rodent model of ELA, we found that male adolescent mice that had been exposed to LB exhibit significant deficits in contextual fear conditioning and synaptic connectivity in the hippocampus, which are not observed in females. This is linked to altered developmental refinement of connectivity, with LB severely impairing microglial-mediated synaptic pruning in the hippocampus of male and female pups on postnatal day 17 (P17), but not in adolescent P33 mice when levels of synaptic engulfment by microglia are substantially lower. Since the rodent hippocampus undergoes intense synaptic pruning during the second and third weeks of life, we investigated whether microglia are required for the synaptic and behavioral aberrations observed in adolescent LB mice. Indeed, transient ablation of microglia from P13-21 in normally developing mice caused sex-specific behavioral and synaptic abnormalities similar to those observed in adolescent LB mice. Furthermore, chemogenetic activation of microglia during the same period reversed the microglial-mediated phagocytic deficits at P17 and restored normal contextual fear conditioning and synaptic connectivity in adolescent LB male mice. Our data support an additional contribution of astrocytes in the sex-specific effects of LB, with increased expression of the membrane receptor MEGF10 and enhanced synaptic engulfment in hippocampal astrocytes of 17-day-old LB females, but not in LB male littermates. These findings suggest a potential compensatory mechanism that may explain the relative resilience of LB females. Collectively, our study highlights a novel role for glial cells in mediating sex-specific hippocampal deficits in a mouse model of ELA.

Exploring the feasibility of linking historical air pollution data to the Christchurch Health and Development study: A birth cohort study in Aotearoa, New Zealand.

Spatial life course epidemiological approaches offer promise for prospectively examining the impacts of air pollution exposure on longer-term health outcomes, but existing research is limited. An essential aspect, often overlooked is the comprehensiveness of exposure data across the lifecourse. The primary objective was to meticulously reconstruct historical estimates of air pollution exposure to include prenatal exposure as well as annual exposure from birth to 10 years (1977-1987) for each cohort member. We linked these data from a birth cohort of 1,265 individuals, born in Aotearoa/New Zealand in mid-1977 and studied to age 40, to historical air pollution data to create estimates of exposure from birth to 10 years (1977-1987). Improvements in air quality over time were found. However, outcomes varied by demographic and socioeconomic factors. Future research should examine how inequitable air pollution exposure is related to health outcomes over the life course.