Early Period Of Life Research Articles

Prenatal chemical exposures and the methylome: current evidence and opportunities for environmental epigenetics.

Exposure to pollutants and chemicals during critical developmental periods in early life can impact health and disease risk across the life course. Research in environmental epigenetics has provided increasing evidence that prenatal exposures affect epigenetic markers, particularly DNA methylation. In this article, we discuss the role of DNA methylation in early life programming and review evidence linking the intrauterine environment to epigenetic modifications, with a focus on exposure to tobacco smoke, metals, and endocrine-disrupting chemicals. We also discuss challenges and novel approaches in environmental epigenetic research and explore the potential of epigenetic biomarkers in studies of pediatric populations as indicators of exposure and disease risk. Overall, we aim to highlight how advancements in environmental epigenetics may transform our understanding of early-life exposures and inform new approaches for supporting long-term health.

The Relationship Between Nutritional Status And The Development Of Children Aged 4-60 Months

Child development is an important aspect of human life, especially in the early period of life, which is often referred to as the critical or golden period as the child's brain undergoes rapid growth. Developmental disorders in children under five, especially in terms of motor skills, have a long-term impact on their development, and a child's nutritional status has been shown to play a role in the process. Therefore, this study aims to determine the relationship between nutritional status and development of children aged 4-60 months in Jember Regency. The research method used was a quantitative correlational approach with a cross-sectional approach, involving a total of 57 children who had a Kartu Menuju Sehat (KMS) as the population. From the results of the formula calculation, the sample size was determined as 50 respondents using a non-randomized (non-probability) method, namely purposive sampling based on certain criteria. The research instruments involved the Kartu Menuju Sehat (KMS) to assess children's nutritional status and the Developmental Pre-Screening Questionnaire (KPSP) to identify children's development. The results of the chi-square statistical test revealed a significant relationship between nutritional status and development of children aged 4-60 months in Jember District. [ Children with good nutritional status show more optimal developmental progress, while children with poor nutritional status tend to experience slower or inappropriate development for their age. This finding supports theories that emphasize the importance of adequate nutrition for children's growth and development. Therefore, efforts to improve children's nutritional status should be a top priority in various child health and education programs. With the right understanding and action, we can help create a healthier and more potential future generation.

Experimental models of antibiotic exposure and atopic disease.

In addition to numerous clinical studies, research using experimental models have contributed extensive evidence to the link between antibiotic exposure and atopic disease. A number of mouse models of allergy have been developed and used to uncover the specific effects of various microbiota members and perturbations on allergy development. Studies in mice that lack microbes entirely have also demonstrated the various components of the immune system that require microbial exposure. The importance of the early-life period and the mechanisms by which atopy "protective" species identified in human cohorts promote immune development have been elucidated in mice. Finally, non-animal models involving human-derived cells shed light on specific effects of bacteria on human epithelial and immune responses. When considered alongside clinical cohort studies, experimental model systems have provided crucial evidence for the link between the neonatal gut microbiota and allergic disease, immensely supporting the stewardship of antibiotic administration in infants. The following review aims to describe the range of experimental models used for studying factors that affect the relationship between the gut microbiota and allergic disease and summarize key findings that have come from research in animal and in vitro models.

Acute Stress Affects the Relaxin/Insulin-Like Family Peptide Receptor 3 mRNA Expression in Brain of Pubertal Male Wistar Rats.

The current literature suggests that relaxin-3/relaxin/insulin-like family peptide receptor 3 (RLN-3/RXFP-3) system is involved in the pathophysiology of affective disorders because the results of anatomical and pharmacological studies have shown that the RLN-3 signaling pathway plays a role in modulating the stress response, anxiety, arousal, depression-like behavior, and neuroendocrine homeostasis. The risk of developing mental illnesses in adulthood is increased by exposure to stress in early periods of life. The available data indicate that puberty is especially characterized by the development of the neural system and emotionality and is a "stress-sensitive" period. The presented study assessed the short-term changes in the expression of RLN-3 and RXFP-3 mRNA in the stress-dependent brain regions in male pubertal Wistar rats that had been subjected to acute stress. Three stressors were applied from 42 to 44 postnatal days (first day: a single forced swim; second day: stress on an elevated platform that was repeated three times; third day: restraint stress three times). Anxiety (open field, elevated plus maze test) and anhedonic-like behavior (sucrose preference test) were estimated during these tests. The corticosterone (CORT) levels and blood morphology were estimated. We found that the RXFP-3 mRNA expression decreased in the brainstem, whereas it increased in the hypothalamus 72h after acute stress. These molecular changes were accompanied by the increased levels of CORT and anxiety-like behavior detected in the open field test that had been conducted earlier, that is, 24h after the stress procedure. These findings shed new light on the neurochemical changes that are involved in the compensatory response to adverse events in pubertal male rats and support other data that suggest a regulatory interplay between the RLN-3 pathway and the hypothalamus-pituitary-adrenal axis activity in the mechanisms of anxiety-like behavior.

Oral tolerance to dietary antigens and Foxp3+ regulatory T cells.

Immune tolerance to foods develops in the intestine upon food ingestion and is essential to prevent IgE-mediated food allergy and gut inflammation. In homeostasis, the intestine is a tolerogenic environment that favors the formation of food-specific Foxp3+ regulatory T cells. A tolerogenic intestinal environment depends on colonization by diverse microbiota and exposure to solid foods at a critical period in early life. These early immune responses lead to the induction of antigen-specific Foxp3+ regulatory T cells in draining mesenteric lymph nodes. These peripherally induced regulatory cells circulate and seed the lamina propria of the gut, exerting suppressive function systemically and locally in the intestine. Successful establishment of a tolerogenic intestinal environment in early life sets the stage for oral tolerance to new antigens in adult life.

Effects of maternal contact and positive human contact during lactation on pork quality: Positive human contact to piglets during lactation improves pork loin muscle pH

Enhancing stress resilience through the early life period in pigs could potentially improve pork quality. It was hypothesised that pigs receiving maternal contact or positive human contact during lactation would have improved carcass and pork quality. Seventy-nine mixed-sex pigs were selected from a 2 × 2 factorial randomised block design for treatments maternal contact (MC+) / reduced maternal contact (MC-); and positive human contact (HC+) / control (HC-). Modified farrowing crates were utilised to reduce maternal contact (MC-). Litters in the HC+ treatment received five minutes of daily positive human interaction (stroking). Treatments ceased at 22 days of age (weaning) and pigs were slaughtered after 21 weeks of age. The m. longissimus thoracis et lumborum pH was higher in HC+ than HC- pigs (P < 0.05) during chilling, from 90 min post slaughter. No HC effects (P > 0.05) were observed for cortisol or haptoglobin concentration, hot carcass weight, P2 backfat, carcass scratches, colour, drip loss, cook loss and shear force. MC+ tended (P < 0.086) to increase carcass weight, P2 and carcass scratch score compared to MC-, but no further impacts were observed. The impact of positive human contact during early life was observed 20+ weeks after treatment with reduced pH decline, potentially indicating a reduction in pre-slaughter stress, however there were no further impacts on pork quality. There is evidence that maternal contact is important for lifetime growth performance of pigs but the impacts on stress resilience are less apparent.

DNA Methylation of PXDN Is Associated with Early-Life Adversity in Adult Mental Disorders.

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities during childhood. Mental disorders are strongly influenced by environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA and the risk of an adult mental disorder is still not fully understood. Evidence is emerging that long-lasting changes in the epigenetic processes regulating gene expression, such as DNA methylation, play an important role in the biological mechanisms linking ELA and mental disorders. Based on a recent study, we analyzed the DNA methylation of a specific CpG site within the gene PXDN-cg10888111-in blood in the context of ELA across a set of psychiatric disorders, namely Borderline Personality Disorder (BPD), Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD), and its potential contribution to their pathogenesis. We found significant hypermethylation in mentally ill patients with high levels of ELA compared to patients with low levels of ELA, whereas cg10888111 methylation in healthy control individuals was not affected by ELA. Further investigations revealed that this effect was driven by the MDD cohort. Providing a direct comparison of cg10888111 DNA methylation in blood in the context of ELA across three mental disorders, our results indicate the role of PXDN regulation in the response to ELA in the pathogenesis of mental disorders, especially MDD. Further studies will be needed to validate these results and decipher the corresponding biological network that is involved in the transmission of ELA to an adult mental disorder in general.

Dietary diversity and associated factors among infants and young children in three West African countries.

Providing children healthy diversified diets is important for their optimal growth and development. The high prevalence of under-nourishment during the critical early life period is of serious concern in West Africa. We assessed the level of dietary diversity and associated factors for children aged 6-23 months in Côte d'Ivoire, Niger and Senegal. Prior 24 h dietary intake was assessed for 3,528 children (Côte d'Ivoire: N = 118; Niger: N = 763; Senegal: N = 2,647) using the Diet Quality Questionnaire survey tool administered to primary caregivers. Cluster random sampling was conducted for urban and rural areas in Niger and Senegal and simple random sampling was used in Côte d'Ivoire, where only rural households were selected. Survey data were analyzed to determine children's intake of items from eight food groups: breast milk; grains, roots, tubers and plantains; pulses, nuts and seeds; dairy products; flesh foods; eggs; vitamin A-rich fruits and vegetables; and other fruits and vegetables. Minimum Dietary Diversity (MDD) was assessed based on the consumption of ≥5 of the 8 food groups. In all countries, the majority of children were ≥ 12 months of age and from rural households. Children from poor/very poor households ranged from 32.4 to 41.9%. MDD prevalence was 54.2% in Côte d'Ivoire, 33.3% in Niger and 30.8% in Senegal. In all three countries, children 12-23 months had significantly higher consumption of six of the food groups, compared to those 6-11 months, and children ≥12 months had a higher likelihood of MDD, compared to infants, in Niger (aOR = 4.25; 95% CI: 2.46, 7.36) and Senegal (aOR = 2.69; 95% CI: 2.15, 3.35). MDD prevalence was higher among children in urban, compared to rural, areas in Niger (p = 0.020) and Senegal (p < 0.001) and significantly higher in the wealthiest, compared to poorest, households. This study suggests most young children in Côte d'Ivoire, Niger and Senegal are not receiving an adequately diversified diet, with a reliance on starchy staples and lower intake of high-quality protein sources. Our results highlight socio-economic barriers to attaining dietary diversity in these settings and stress the urgent and continuing need for investments in strategies that support optimal complementary feeding practices.

Bone mineral density and geometric morphometrics: Indicators of growth in the immature pars basilaris

The pars basilaris forms a central component of the immature basicranium and owing to its resilience to post-mortem and taphonomic changes, holds significance across evolutionary, clinical, and forensic contexts. While size and shape parameters of the pars basilaris have been investigated, little is known about the influence of the underlying bone mineral density on the morphometry of this bone during growth. This study aimed to investigate the development and growth of the pars basilaris with specific reference to changes in bone density patterning and development of osteological features, during the prenatal and early postnatal periods of life. A total of 109 pars basilari were sourced from the Johannesburg Forensic Paediatric Collection, University of the Witwatersrand, South Africa. The study sample was subdivided into early prenatal (<30 gestational weeks), prenatal (30–40 gestational weeks) and postnatal (birth to 7.5 months) groups and micro-CT scanned to assess bone mineral density patterns across seven regions of interest. Size and shape changes were analysed using 11 digitized landmarks and geometric morphometrics. When comparing across age groups, the assessed dimensions increased with growth manifesting as a deepening at the anterior border of the foramen magnum, development of the lateral angles and widening of the bone at the lateral projections and spheno-occipital synchondrosis. However, no significant changes in the distribution of bone mineral density were observed. An appreciation of morphological changes and bone quality at specific growth sites in the pars basilaris is essential when analyzing remains of unknown provenance for the purposes of identification in disaster victim settings.

Experience-dependent MAPK/ERK signaling in glia regulates critical period remodeling of synaptic glomeruli

Early-life critical periods allow initial sensory experience to remodel brain circuitry so that synaptic connectivity can be optimized to environmental input. In the Drosophila juvenile brain, olfactory sensory neuron (OSN) synaptic glomeruli are pruned by glial phagocytosis in dose-dependent response to early odor experience during a well-defined critical period. Extracellular signal-regulated kinase (ERK) separation of phases-based activity reporter of kinase (SPARK) biosensors reveal experience-dependent signaling in glia during this critical period. Glial ERK-SPARK signaling is depressed by removal of Draper receptors orchestrating glial phagocytosis. Cell-targeted genetic knockdown of glial ERK signaling reduces olfactory experience-dependent glial pruning of the OSN synaptic glomeruli in a dose-dependent mechanism. Noonan Syndrome is caused by gain-of-function mutations in protein tyrosine phosphatase non-receptor type 11 (PTPN11) inhibiting ERK signaling, and a glial-targeted patient-derived mutation increases experience-dependent glial ERK signaling and impairs experience-dependent glial pruning of the OSN synaptic glomeruli. We conclude that critical period experience drives glial ERK signaling that is required for dose-dependent pruning of brain synaptic glomeruli, and that altered glial ERK signaling impairs this critical period mechanism in a Noonan Syndrome disease model.

Early-Neonatal, Late-Neonatal, Postneonatal, and Child Mortality Rates Across India, 1993-2021

The global success of the child survival agenda depends on how rapidly mortality at early ages after birth declines in India, and changes need to be monitored to evaluate the status. To understand the disaggregated patterns of decrease in early-life mortality across states and union territories (UTs) of India. Repeated cross-sectional data from the 5 rounds of the National Family Health Survey conducted in 1992-1993, 1998-1999, 2005-2006, 2015-2016, and 2019-2021 were used in a representative population-based study. The study was based on data of children born in the past 5 years with complete information on date of birth and age at death. The analysis was conducted in February 2024. Time and geographic units. Mortality rates were computed for 4 early-life periods: early-neonatal (first 7 days), late-neonatal (8-28 days), postneonatal (29 days to 11 months), and child (12-59 months). For early and late neonatal periods, the rates are expressed as deaths per 1000 live births, for postneonatal, as deaths per 1000 children aged at least 29 days and for child, deaths per 1000 children aged at least 1 year. These are collectively mentioned as deaths per 1000 for all mortalities. The relative burden of each of the age-specific mortalities to total mortality in children younger than 5 years was also computed. The final analytical sample included 33 667 (1993), 29 549 (1999), 23 020 (2006), 82 294 (2016), and 64 242 (2021) children who died before their fifth birthday in the past 5 years of each survey. Mortality rates were lowest for the late-neonatal and child periods; early-neonatal was the highest in 2021. Child mortality experienced the most substantial decrease between 1993 and 2021, from 33.5 to 6.9 deaths per 1000, accompanied by a substantial reduction in interstate inequalities. While early-neonatal (from 33.5 to 20.3 deaths per 1000), late-neonatal (from 14.1 to 4.1 deaths per 1000), and postneonatal (from 31.0 to 10.8 deaths per 1000) mortality also decreased, interstate inequalities remained notable. The mortality burden shifted over time and is now concentrated during the early-neonatal (48.3% of total deaths in children younger than 5 years) and postneonatal (25.6%) periods. A stagnation or worsening for certain states and UTs was observed from 2016 to 2021 for early-neonatal, late-neonatal, and postneonatal mortality. If this pattern continues, these states and UTs will not meet the United Nations Sustainable Development Goal targets related to child survival. In this repeated cross-sectional study of 5 time periods, the decrease in mortality during early-neonatal and postneonatal phases of mortality was relatively slower, with notable variations across states and UTs. The findings suggest that policies pertaining to early-neonatal and postneonatal mortalities need to be prioritized and targeting of policies and interventions needs to be context-specific.

Mental causation: an evolutionary perspective.

The relationship between consciousness and individual agency is examined from a bottom-up evolutionary perspective, an approach somewhat different from other ways of dealing with the issue, but one relevant to the question of animal consciousness. Two ways are identified that would decouple the two, allowing consciousness of a limited kind to exist without agency: (1) reflex pathways that incorporate conscious sensations as an intrinsic component (InCs), and (2) reflexes that are consciously conditioned and dependent on synaptic plasticity but not memory (CCRs). Whether InCs and CCRs exist as more than hypothetical constructs is not clear, and InCs are in any case limited to theories where consciousness depends directly on EM field-based effects. Consciousness with agency, as we experience it, then belongs in a third category that allows for deliberate choice of alternative actions (DCs), where the key difference between this and CCR-level pathways is that DCs require access to explicit memory systems whereas CCRs do not. CCRs are nevertheless useful from a heuristic standpoint as a conceptual model for how conscious inputs could act to refine routine behaviors while allowing evolution to optimize phenomenal experience (i.e., qualia) in the absence of individual agency, a somewhat counterintuitive result. However, so long as CCRs are not a required precondition for the evolution of memory-dependent DC-level processes, the later could have evolved first. If so, the adaptive benefit of consciousness when it first evolved may be linked as much to the role it plays in encoding memories as to any other function. The possibility that CCRs are more than a theoretical construct, and have played a role in the evolution of consciousness, argues against theories of consciousness focussed exclusively on higher-order functions as the appropriate way to deal with consciousness as it first evolved, as it develops in the early postnatal period of life, or with the conscious experiences of animals other than ourselves. An evolutionary perspective also resolves the problem of free will, that it is best treated as a property of a species rather than the individuals belonging to that species whereas, in contrast, agency is an attribute of individuals.

A novel useful marker in the early discrimination of transient hyperthyrotropinemia/hypothyroxinemia and congenital hypothyroidism in preterm infants: thyroid-stimulating hormone/free thyroxine ratio.

Transient hyperthyrotropinemia/transient hypothyroxinaemia and congenital hypothyroidism (CH) have completely different treatment and clinical outcomes. However, a powerful, highly sensitive and cost-effective marker for the differentiation of these clinical entities in the early postnatal period is not available. Therefore, we aimed to test the potential, early predictive, diagnostic power of the thyroid-stimulating hormone (TSH)/free thyroxine (fT4) ratio for differentiation of the two clinical entities in the early period of life. TSH and fT4 levels were recorded on the postnatal day 7 of premature infants<32weeks of gestational age. TSH/fT4 ratio was calculated. The significance degree of TSH/fT4 ratio was analyzed for the differentiation of transient hyperthyrotropinemia or transient hypothyroxinaemia and CH. The study included 1,204 preterm infants<32weeks of gestational age. Of the 1,204 infants, 978 (81.2 %) had normal thyroid function. Eighty-eight infants (7.3 %) were diagnosed with CH and 138 (11.5 %) with transient hyperthyrotropinemia or transient hypothyroxinemia. Initial TSH/fT4 ratio>4.8 was found to be an early diagnostic warning sign with high power in favor of transient hyperthyrotropinemia or transient hypothyroxinemia (AUC value: 0.947) and TSH/fT4 ratio>12.5 (AUC value: 0.999) was found to be an early diagnostic warning sign with high power in favor of CH (p=0.0001). We found for the first time that the TSH/fT4 ratio can be used for the early differentiation of transient hyperthyrotropinemia/transient hypothyroxinaemia and CH in preterm infants without additional cost and with high power.

The Yin and Yang of the oxytocin and stress systems: opposites, yet interdependent and intertwined determinants of lifelong health trajectories.

During parturition and the immediate post-partum period there are two opposite, yet interdependent and intertwined systems that are highly active and play a role in determining lifelong health and behaviour in both the mother and her infant: the stress and the anti-stress (oxytocin) system. Before attempting to understand how the environment around birth determines long-term health trajectories, it is essential to understand how these two systems operate and how they interact. Here, we discuss together the hormonal and neuronal arms of both the hypothalamic-pituitary-adrenal (HPA) axis and the oxytocinergic systems and how they interact. Although the HPA axis and glucocorticoid stress axis are well studied, the role of oxytocin as an extremely powerful anti-stress hormone deserves more attention. It is clear that these anti-stress effects depend on oxytocinergic nerves emanating from the supraoptic nucleus (SON) and paraventricular nucleus (PVN), and project to multiple sites at which the stress system is regulated. These, include projections to corticotropin releasing hormone (CRH) neurons within the PVN, to the anterior pituitary, to areas involved in sympathetic and parasympathetic nervous control, to NA neurons in the locus coeruleus (LC), and to CRH neurons in the amygdala. In the context of the interaction between the HPA axis and the oxytocin system birth is a particularly interesting period as, for both the mother and the infant, both systems are very strongly activated within the same narrow time window. Data suggest that the HPA axis and the oxytocin system appear to interact in this early-life period, with effects lasting many years. If mother-child skin-to-skin contact occurs almost immediately postpartum, the effects of the anti-stress (oxytocin) system become more prominent, moderating lifelong health trajectories. There is clear evidence that HPA axis activity during this time is dependent on the balance between the HPA axis and the oxytocin system, the latter being reinforced by specific somatosensory inputs, and this has long-term consequences for stress reactivity.

Associations of radiologic characteristics of the neonatal hypothalamus with early life adiposity gain.

The mediobasal hypothalamus (MBH) is a key brain area for regulation of energy balance. Previous neuroimaging studies suggest that T2-based signal properties indicative of cellular inflammatory response (gliosis) are present in adults and children with obesity, and predicts greater adiposity gain in children at risk of obesity. The current study aimed to extend this concept to the early life period by considering if, in full-term healthy neonates (up to n = 35), MRI evidence of MBH gliosis is associated with changes in early life (neonatal to six months) body fat percentage measured by DXA. In this initial study, neonatal T2 signal in the MBH was positively associated with six-month changes in body fat percentage. This finding supports the notion that underlying processes in the MBH may play a role in early life growth and, by extension, childhood obesity risk.

Infrared thermography as a potential non-invasive tool to study seasonal stress in late gestation Sahiwal cows and their neonate calves

Stress triggers a multitude of physiological responses including alterations in surface temperature aimed at maintaining homeostasis of animal. The present study was undertaken to evaluate the comparative seasonal effect of thermal stress on body surface temperature during the critical period of late gestation and early life. For this, late gestational Sahiwal cows (n=48) were selected and categorized into four groups: natural heat stressed (NHS), cooling treated (CLT), spring and winter groups, and their neonate calves born in summer (IUHS-intra uterine heat stressed and IUCL-intra uterine cooled), spring and winter season. The thermal profile obtained from infrared thermography (IRT) showed a trend of surface temperature for each region examined over varied THI (temperature humidity index). Body surface temperature in NHS was significantly higher, followed by spring, CLT and least in winter group cows. Within the group, study revealed numerically high surface temperature of eye, front and udder on the day of parturition, while slightly lower temperature of flank portion. NHS, CLT and spring cows had non-significant variations in udder temperature. Insulation breakage from the legs at a colder temperature was observed. In neonates, significantly high surface temperature was observed in IUHS, followed by IUCL and spring calves, while significantly low surface temperature in winter calves. Thus, cooling treatment in the late gestation significantly lowered body surface temperature in both dams and calves. Further, it is also concluded that out of different anatomical regions, eye and feet temperature is the most reliable indicator for assessing seasonal stress with changing THI.

Association between early life exposure to agriculture, biodiversity, and green space and risk of inflammatory bowel disease: a population-based cohort study

Specific pollutants and environmental exposures are implicated in modulating inflammatory bowel disease (IBD) risk. However, the role of environmental exposures, particularly during the early life period, towards IBD risk, has not been systematically evaluated. We conducted a nationwide population-based cohort study during the study period extending from January 1, 1995, to September 1, 2020, using cross-linked Danish registers, maps, and inventories to ascertain the impact of agricultural land use, biodiversity, green space, urban space, blue space, and normalized difference vegetation index during pregnancy and the first two years of life on IBD, Crohn's disease (CD), and ulcerative colitis (UC) risk, using adjusted Cox proportional hazards regression analyses. We adjusted for covariates sex, maternal age at delivery, calendar year of birth, municipal-level socioeconomic status, and first-degree relative with IBD. Of 1,438,487 individuals included in the study who were followed from age 2 years until a median (IQR) age of 14 (8-20) years, 3768 individuals were diagnosed with IBD. Exposure to the second, third and highest quartiles of agriculture land use during early life, relative to the lowest quartile, were associated with increased CD risk (aHR 1.12, 95% CI 1.01, 1.26, 1.19, 95% CI 1.05, 1.34 and, 1.24 95% CI 1.06, 1.46, respectively). There was no association of agriculture land use with UC risk. Conversely, exposure to the third quartile of biodiversity in early life, compared to the lowest quartile, were associated with a lower CD risk (aHR 0.86, 95% CI 0.75, 0.98). A protective effect of greenspace was noted in the highest quartile for CD (aHR 0.87, 95% CI 0.78, 0.98). In a nationwide cohort with long-term follow up data, early life environmental exposures were associated with modulation of CD risk, with a harmful effect of agriculture land use and protective effect of biodiversity and green space. Danish National Research Foundation, the International Organization for the Study of Inflammatory Bowel Disease, the National Institute of Diabetes and Digestive and Kidney Diseases.

Experience-Dependent Remodeling of Juvenile Brain Olfactory Sensory Neuron Synaptic Connectivity in an Early-Life Critical Period.

Early-life olfactory sensory experience induces dramatic synaptic glomeruli remodeling in the Drosophila juvenile brain, which is experientially dose-dependent, temporally restricted, and transiently reversible only in a short, well-defined critical period. The directionality of brain circuit synaptic connectivity remodeling is determined by the specific odorant acting on the respondent receptor class of olfactory sensory neurons. In general, each neuron class expresses only a single odorant receptor and innervates a single olfactory synaptic glomerulus. In the Drosophila genetic model, the full array of olfactory glomeruli has been precisely mapped by odorant responsiveness and behavioral output. Ethyl butyrate (EB) odorant activates Or42a receptor neurons innervating the VM7 glomerulus. During the early-life critical period, EB experience drives dose-dependent synapse elimination in the Or42a olfactory sensory neurons. Timed periods of dosed EB odorant exposure allow investigation of experience-dependent circuit connectivity pruning in juvenile brain. Confocal microscopy imaging of antennal lobe synaptic glomeruli is done with Or42a receptor-driven transgenic markers that provide quantification of synapse number and innervation volume. The sophisticated Drosophila genetic toolkit enables the systematic dissection of the cellular and molecular mechanisms mediating brain circuit remodeling.

The contingent animal: does artificial innateness misrepresent behavioral development?

While organisms are continually experiencing and interacting with their environments, the role and extent of experiences in behavioral development has been controversial. Some argue that adaptive behaviors are acquired through experiences, while others claim they are the result of innate programs that don’t require environmental input. Such controversies have historically occurred within animal behavior and psychology, but similar debates are emerging in the field of artificial intelligence. Here, the debate is centered on those who design experience-dependent systems that are trained to learn the statistical properties of “environmental” inputs, and those advocating the use of pre-packaged artificially “innate” responses tailored to prespecified inputs. Those favoring artificial innateness draw analogies with animal behavior to argue that innateness is necessary for the emergence of complex adaptive behavior. But does behavioral development in animals reflect the unfolding of innate programs? Here we highlight the widespread role of specifically causal experiences in the ontogeny of species-typical behaviors. All behaviors are an outcome of a chain of organism-environment transactions—called ontogenetic niches—that begin in the earliest periods of life. This challenges the notion that organisms come prepared with innate programs for behavior. We suggest that an artificial intelligence that matches the complexity of animal behavior should be based on principles of behavioral development, where experiences are necessary and specifically causal factors in the emergence of behavioral abilities.

A34 DEVELOPING A NOVEL MOUSE MODEL TO ELUCIDATE MECHANISMS OF ORAL TOLERANCE IN EARLY LIFE

Abstract Background Oral tolerance is the active suppression of immune responses to antigens that are first encountered in the gastrointestinal tract. When this process fails, food allergies can arise. Food allergies affect up to 6% of Canadian children underlining the need for a thorough understanding of how oral tolerance develops in childhood. Despite this, tolerance has historically been studied using adult rodent models instead of focusing on more physiologically relevant early-life time points. Aims Our research aims to develop a robust mouse model to elucidate mechanisms of oral tolerance development in early life and we hypothesize that the mesenteric lymph nodes are a major site of food antigen-specific T cell development in early life. Methods Prior to weaning, actively suckling mouse pups were orally gavaged with ovalbumin (OVA), an egg white component and common food allergen or water as a control. Following a series of systemic challenges with OVA, circulating antibody levels were quantified by ELISA to measure the development of oral tolerance to OVA. Additionally, splenocytes isolated from tolerized and control mice were stimulated in vitro with exogenous OVA and cytokines were quantified in culture supernatants via a cytometric bead array assay to assess the suppression of T cell responses to OVA in tolerized mice. One week following oral OVA exposure flow cytometry was used to characterize the expansion of T cell populations in the mesenteric lymph nodes, spleen and thymus. Results Mice orally gavaged with OVA in early life show reduced systemic antibody production after subsequent challenges with OVA, compared to mice not orally exposed to OVA. We determined the minimum dosage of OVA required to confer tolerance in these mice and confirmed the validity of this model in both male and female C57BL/6 and BALB/c mice. Further, we detected an active suppression of IL-5 production, a cytokine indicative of a Type 2 immune response, in OVA-stimulated splenocyte cultures isolated from mice tolerized to OVA. We found a significant increase in the frequency of CD4 T cells in the mesenteric lymph nodes just 1-week following oral OVA exposure. Conclusions We have developed a robust mouse model of oral tolerance where mice are directly exposed to OVA in an early life period while they are still actively ingesting breastmilk, and their mucosal immune system and intestinal microbiota composition are under significant development. To date, our data suggests that the gut draining mesenteric lymph nodes may be a site of food antigen-specific T cell expansion in early life. Funding Agencies CIHRTRIANGLE