Critical Developmental Period Research Articles

Effects of Task Interference on Kinematics and Dual-Task Cost of Running in Early Childhood.

Children aged 3-8 are in a critical period for motor development and postural control. Running is a basic motor skill that children need to master in early childhood. While running, children are prone to dangerous events such as falls. This study investigates the kinematic characteristics of running by children associated with different interference tasks, i.e., normalized running, cognitive dual-tasks, and obstacle crossing tasks, and provides a theoretical foundation for the interference mechanism of children's dynamic postural control and for screening of motor disorders. Two hundred children aged 3-8 were recruited. The BTS Bioengineering infrared motion capture system was used to collect spatiotemporal and kinematic running data under three tasks. Repeated measures of variance analysis were used to compare the effects of different interference tasks and ages on children's running signs. The main and interaction effect tests were compared by the Bonferroni method. The results and conclusions are as follows: (1) Running characteristics of early childhood are influenced by interference tasks and age. With interference tasks, the overall characteristics of running by children aged 3-8 showed an increasing trend in running cycle time and a decreasing trend in stride length, step length, cadence, and speed. (2) Both cognitive and obstacle crossing tasks had costs, and cognitive task costs were greater than obstacle crossing costs. Children adopted a "task first" running strategy with different interference tasks. When facing cognitive tasks, their overall joint motion decreased, and they reduced joint motions to promote task completion. When facing obstacle crossing tasks, because of the characteristics of the task itself, children increased joint motions to cope with interference. (3) In terms of age, the running characteristics showed a nonlinear development trend in various indicators, with a degree of recurrence and high variability in adjacent age groups. (4) The dual-task interference paradigm of "postural-cognition" can be used as a motor intervention tool to promote the development of basic motor skills in early childhood.

Morphological features of the poultry thymus

This article reviews the literature on the morphological features of the poultry thymus. Since the preservation of livestock and disease prevention is a constant problem, the issue of poultry care will always remain in the forefront. Efforts to preserve the population and increase their productivity are directly related to strengthening poultry immunity and the state of their immune system. The study of the morphology of immune system organs allows us to objectively assess the effectiveness of methods for the prevention and treatment of various diseases, as well as to identify critical periods of development of the immune system and the body as a whole. When assessing the immune status of poultry, much attention is paid to the state of lymphoid organs, including the thymus. Currently, aspects related to the dynamics of development of immunocompetent organs during the postnatal period of ontogenesis and the time frame of their involution remain unresolved. Understanding the morphological features of the thymus and its changes is a key element in assessing the function of the immune system. It was found that with the growth and development of chicks, the absolute and relative weight of the thymus increases. However, at the onset of reproductive maturity, these values decrease significantly. Involution of the thymus mass occurs, the boundary between cortical and cerebral substances becomes less distinct, and the cellular composition of the thymus changes. The process of age-related involution is accompanied by a decrease in lymphoid tissue and T-lymphocytes. It is worth noting that the total number of circulating T-lymphocytes remains stable, as this population includes long-lived cells that do not require constant renewal. In this context, there is a change in the ratio of cortical and cerebral substances, the growth of connective tissue stroma and adipose tissue. It is noted that stress factors are one of the causes of early thymic involution, and the degree of development and morphological state of the thymus significantly affect the body's resistance to infections. Changes in the structure and morphometry of the chicken thymus can be an important criterion for the morphological diagnosis of immunodeficiencies in poultry.

Knowns and unknowns about the neurobiology of stuttering.

Stuttering occurs in early childhood during a dynamic phase of brain and behavioral development. The latest studies examining children at ages close to this critical developmental period have identified early brain alterations that are most likely linked to stuttering, while spontaneous recovery appears related to increased inter-area connectivity. By contrast, therapy-driven improvement in adults is associated with a functional reorganization within and beyond the speech network. The etiology of stuttering, however, remains enigmatic. This Unsolved Mystery highlights critical questions and points to neuroimaging findings that could inspire future research to uncover how genetics, interacting neural hierarchies, social context, and reward circuitry contribute to the many facets of stuttering.

The effects of prolonged pacifier use on language development in infants and toddlers.

Pacifiers are a common soothing tool used by parents to calm and comfort infants and toddlers. While pacifiers can provide temporary relief, there is growing concern about the potential long-term effects of prolonged pacifier use on language and cognitive development. Previous studies have suggested that prolonged use of pacifiers may have negative consequences on language outcomes in infants and toddlers, especially during the first few years of life known to be a critical period for language development. Previous studies have shown that children who use pacifiers extensively have smaller vocabulary sizes at 1 and 2 years of age which can have subsequent effects on socioemotional. In addition, significant association between greater frequency of daytime pacifier use and worsening of cognitive outcomes was shown. Furthermore, research has shown a strong dose-response association between intense pacifier use up to 4 years of age and lower IQ at 6 years. Recently, the importance of oral motor movements and sensorimotor production for speech perception in infants as young as 6 months has been highlighted, raising important questions on the effect of oral motor movement restrictions at an early age. Together, these findings raise concern about the potential long-term effects of prolonged pacifier use on language and cognitive development at a critical time in child development. However, it is still debatable within the scientific field the potential relationship between pacifier use and language development in early life most likely due to the complexity of studying child development. This mini review aims to provide valuable insights for parents, caregivers, and healthcare professionals in making informed decisions and understand regarding pacifier use for infants and toddlers.

IMPLEMENTATION OF STUNTING REDUCTION REGULATIONS AND POLICIES IN EAST LOMBOK REGENCY, INDONESIA

Objective: This research aims to develop a theoretical model for implementing stunting management policies applicable in East Lombok Regency, Indonesia, and other districts with high stunting prevalence across Indonesia through the enactment of statutory regulations. The study focuses on community engagement, cross-sector collaboration, and capacity building. Theoretical framework: Drawing upon the Network Policy Model concept and supported by the Social-Ecological Model from USAID. Methodology: Employing a qualitative approach, the research utilizes a phenomenological study of stunting incidents, complemented by focus group discussions and interviews. Field observations are integrated to validate the data. Research is conducted in 11 intervention and 10 non-intervention sub-districts. Results: The 2023 intervention exhibited a significant decrease in stunting prevalence from 17.46% (2022) to 14.22% and wasting rate from 5.93% (2022) to 5.07%. Four aspects of success emerged: mapping of stunting areas, improved regulations, community involvement, and collaborative education programs. Conclusion: Successful stunting and wasting management in 11 sub-districts in East Lombok Regency began with intervention mapping. Government collaboration with SEAMEO RECFON, UNICEF, and universities was pivotal. Regulatory improvements included strengthening marriage regulations and school regulations. Community involvement and collaborative education programs were vital, ensuring comprehensive program implementation. Recommendation: The five recommendations from this research are strengthening community involvement by encouraging active participation, improving the governance structure, enhancing capacity building by continuing and expanding training initiatives for the organization's regional representatives, and fostering cross-sector collaboration by strengthening partnerships between regional organizations, NGOs, academic institutions, and international organizations; collaborative efforts can leverage diverse expertise, resources, and networks to accelerate efforts to reduce stunting and prevent wasting; promoting nutrition education and outreach: implement comprehensive nutrition education programs targeting schools, communities, and families. Emphasize the importance of a balanced diet, breastfeeding practices, and proper nutrition during critical periods of growth and development. Research Implications: The findings inform policymakers, program managers, and stakeholders involved in stunting reduction efforts in East Lombok Regency, facilitating evidence-based decision-making and program design for more effective and sustainable interventions. Originality/Value: This research contributes to the existing literature on stunting reduction by providing empirical evidence and insights using the Network Policy Model concept and the Social-Ecological Model. The study's contextual specificity, methodological rigor, stakeholder engagement, and multiple perspectives enrich the understanding of stunting management initiatives.

The Effect of Baby Gym on Improving Baby Development in Purwakarta Regency, Indonesia

Introduction: Infancy is a critical period for physical, cognitive, and social-emotional development. Baby gym is a stimulation program designed to improve baby development through various physical, sensory, and social activities. This research aims to analyze the effectiveness of baby gym in improving baby development in Purwakarta Regency, Indonesia.
 Methods: Quasi-experimental research design with pre-test and post-test. A sample of 60 babies aged 6-12 months was divided into two groups: intervention (n=30) who participated in the baby gym program for 3 months and controls (n=30) who did not participate in the baby gym program. Infant development was measured using the Denver developmental screening test (DDST) before and after intervention.
 Results: There was a significant difference in the development of babies in the intervention group compared to the control group (p<0.05). The intervention group showed a higher increase in the DDST total score and gross motor, fine motor, language, and personal social subdomains.
 Conclusion: The baby gym program is effective in improving baby development in Purwakarta Regency, Indonesia.

Directionality explored: Black Adolescents' awareness of systemic racism and race-based experiences.

Increases in conversations about race and racial discrimination experiences during adolescence make this a critical developmental period to investigate adolescents' awareness of racism. We examined bidirectional associations between race-based experiences and awareness of systemic racism-operationalized as understanding systemic causes of racial disparities in education. Adolescents who self-identified as African American/Black were surveyed in Grade 6 (n = 317; Mage = 11.12; 48% girls) and Grade 8 (n = 247; Mage = 13.15; 56% girls). Cross-lagged panel analyses revealed that racial barrier messages, but not racial discrimination experiences, in Grade 6 positively predicted awareness of systemic racism in Grade 8. Adolescents' awareness of systemic racism in Grade 6 did not predict racial socialization or racial discrimination experiences in Grade 8.

Associations between problem technology use, life stress, and self-esteem among high school students

BackgroundAdolescence is a critical period for development, with many risk factors resulting in long-term health consequences, particularly regarding mental health. The purpose of this study was to examine the associations between problem technology use, life stress, and self-esteem in a representative sample of adolescents residing in Ontario, Canada.MethodsSelf-reported data were obtained from a cross-sectional sample of 4,748 students (57.9% females) in grades 9 to 12 (mean age: 15.9 ± 1.3 years) who participated in the 2019 Ontario Student Drug Use and Health Survey. Problem technology use was measured using the 6-item Short Problem Internet Use Test, life stress was assessed using an item from the British Columbia Adolescent Health Survey and self-esteem was assessed using a global measure from the Rosenberg Self-Esteem Scale. Ordinal logistic regression models were adjusted for age, sex, ethnoracial background, subjective socioeconomic status, body mass index z-score, tobacco cigarette smoking, alcohol consumption and cannabis use.ResultsWe found that 18.3% of participants reported symptoms of moderate-to-high problem technology use, although symptoms were more common in females than males (22% vs. 14.7%, respectively). Moderate-to-high problem technology use was associated with 2.04 (95% CI: 1.77–2.35) times higher odds of reporting high life stress and 2.08 (95% CI: 1.76–2.45) times higher odds of reporting low self-esteem compared to all other response options.ConclusionsFindings from this study show that problem technology use is strongly associated with higher life stress and lower self-esteem in adolescents. This study supports the importance of developing and implementing effective strategies that help to mitigate the adverse effects of problem technology use on adolescent mental health.

Use of Nicotine-Containing Products During Pregnancy: Effects on Fetal Development

Currently, the usage of tobacco products among adult females is prevalent, representing 10 out of 100 adult females (CDC, 2023). In addition, 4.0% of adult women have been reported as using e-cigarettes. This is mainly due to the addiction to nicotine, which releases dopamine in the brain, ultimately causing the user to want to consume more nicotine-containing products. When used during pregnancy, nicotine-containing products could be harmful to both the mother and the growing fetus. Nicotine consumption during pregnancy may impact the critical brain development period of the fetus, thus resulting in several serious birth defects. Among those who use nicotine-containing products, Nicotine Replacement Therapy (NRT) may be used to facilitate reducing addiction to nicotine. NRT can be used as an ideal therapy to help quit smoking tobacco or e-cigarettes as it replaces much of the nicotine in nicotine-containing products, thus decreasing motivation to use tobacco. Despite the reduced nicotine levels, NRT is reported to show that it may pose a threat when used during pregnancy. As a whole, a few studies have revealed the potential detrimental connection between the usage of nicotine-containing products - including tobacco, e-cigarettes, and NRT - during pregnancy and its effects on the fetus. In spite of this, there has been little research done on the subject, which may lead to further complications if the public is largely unaware. This literature review aims to investigate the effects of nicotine-containing products on the developing fetus.

Food security status and cardiometabolic health among pregnant women in the United States.

Pregnant women and their offspring are particularly vulnerable to food insecurity and its adverse effects during critical periods of fetal development. Racially/ethnically minoritized women in the United States (US) who are pregnant are additionally burdened by food insecurity, which may exacerbate cardiovascular health (CVH) disparities. Despite heightened social vulnerability, few studies have employed an intersectional framework, including race and gender, to assess the food insecurity and CVH relationship. We used 2012-2018 and 2020 National Health Interview Survey data among US pregnant women aged 18-49 years old (N = 1,999) to assess the prevalence of food insecurity status by race/ethnicity and to investigate household food security status in relation to ideal CVH, using a modified ideal CVH (mICVH) metric. We categorized food security status as "very low/low", "marginal", or "high". To assess mICVH, a summary score of 7 clinical characteristics and health behaviors was dichotomized as yes [(7)] vs. no [<7]. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of associations between food security status and mICVH were estimated using Poisson regression with robust variance. Models were adjusted for age, household income, educational attainment, geographic region, marital status, alcohol consumption, survey year, and race/ethnicity (in overall model). The mean age ± standard error was 29.0 ± 0.2 years. Among pregnant women, 12.7% reported "very low/low", 10.6% reported "marginal", and 76.7% reported "high" food security. "Very low/low" food security prevalence was higher among NH-Black (16.2%) and Hispanic/Latina (15.2%) pregnant women compared to NH-White (10.3%) and NH-Asian (3.2%) pregnant women. The mICVH prevalence was 11.6% overall and 14.5% for NH-White, 4.1% for NH-Black, 5.0% for Hispanic/Latina, and 26.7% for NH-Asian pregnant women. Among all pregnant women, "very low/low" and "marginal" vs. "high" food security status was associated with a lower prevalence of mICVH {[PRvery low/low = 0.26 (95% CI: 0.08-0.75)]; [PRmarginal = 0.47 (95% CI: 0.23 -0.96)]}. Household food insecurity was higher among pregnant women in minoritized racial/ethnic groups and was associated with lower mICVH prevalence. Given the higher burden of food insecurity among minoritized racial/ethnic groups, food security may be an important intervention target to help address disparities in poor CVH among pregnant women.

Prevalence of Children Aged 6 to 23 Months Who Did Not Consume Animal Milk, Formula, or Solid or Semisolid Food During the Last 24 Hours Across Low- and Middle-Income Countries

The introduction of solid or semisolid foods alongside breast milk plays a vital role in meeting nutritional requirements during early childhood, which is crucial for child growth and development. Understanding the prevalence of zero-food children (defined for research purposes as children aged 6 to 23 months who did not consume animal milk, formula, or solid or semisolid food during the last 24 hours) is essential for targeted interventions to improve feeding practices. To estimate the percentage of zero-food children in 92 low- and middle-income countries. This cross-sectional study analyzed nationally representative cross-sectional household data of children aged 6 to 23 months from the Demographic and Health Surveys and the Multiple Indicator Cluster Surveys conducted between May 20, 2010, and January 27, 2022. Data were obtained from 92 low- and middle-income countries. Standardized procedures were followed to ensure data comparability and reliability. Both percentage and number of zero-food children were estimated. The outcome studied was defined as a binary variable indicating children aged 6 to 23 months who had not been fed any animal milk, formula, or solid or semisolid foods during the 24 hours before each survey, as reported by the mother or caretaker. A sample of 276 379 children aged 6 to 23 months (mean age, 14.2 months [95% CI, 14.15-14.26 months]) in 92 low- and middle-income countries was obtained, of whom 51.4% (95% CI, 51.1%-51.8%) were boys. The estimated percentage of zero-food children was 10.4% (95% CI, 10.1%-10.7%) in the pooled sample, ranging from 0.1% (95% CI, 0%-0.6%) in Costa Rica to 21.8% (95% CI, 19.3%-24.4%) in Guinea. The prevalence of zero-food children was particularly high in West and Central Africa, where the overall prevalence was 10.5% (95% CI, 10.1%-11.0%), and in India, where the prevalence was 19.3% (95% CI, 18.9%-19.8%). India accounted for almost half of zero-food children in this study. In this cross-sectional study of 276 379 children aged 6 to 23 months, substantial disparities in the estimates of food consumption across 92 low- and middle-income countries were found. The prevalence of zero-food children underscores the need for targeted interventions to improve infant and young child feeding practices and ensure optimal nutrition during this critical period of development. The issue is particularly urgent in West and Central Africa and India.

Combined Effect of Maternal Separation and Early-Life Immune Activation on Brain and Behaviour of Rat Offspring.

Adversity during early life, a critical period for brain development, increases vulnerability and can have a lasting impact on the brain and behaviour of a child. However, the long-term effects of cumulative early-life stressors on brain and behaviour are not well known. We studied a 2-hit rat model of early-life adversity using maternal separation (MS) and immune activation (lipopolysaccharide (LPS)). Rat pups underwent MS for 15 (control) or 180 (MS) minutes per day from postnatal day (P)2-14 and were administered saline or LPS (intraperitoneal) on P3. Open-field (OFT) and object-place recognition tests were performed on rat offspring at P33-35 and P42-50, respectively. The pre-frontal cortex (PFC) and hippocampus were removed at the experimental endpoint (P52-55) for mRNA expression. MS induced anxiety-like behaviour in OFT in male and reduced locomotor activity in both male and female offspring. LPS induced a subtle decline in memory in the object-place recognition test in male offspring. MS increased glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor expression in PFC and ionised calcium-binding adapter molecule-1 expression in male hippocampus. MS and LPS resulted in distinct behavioural phenotypes in a sex-specific manner. The combination of MS and LPS had a synergistic effect on the anxiety-like behaviour, locomotor activity, and GFAP mRNA expression outcomes.

Olfactory Critical Periods: How Odor Exposure Shapes the Developing Brain in Mice and Flies.

Neural networks have an extensive ability to change in response to environmental stimuli. This flexibility peaks during restricted windows of time early in life called critical periods. The ubiquitous occurrence of this form of plasticity across sensory modalities and phyla speaks to the importance of critical periods for proper neural development and function. Extensive investigation into visual critical periods has advanced our knowledge of the molecular events and key processes that underlie the impact of early-life experience on neuronal plasticity. However, despite the importance of olfaction for the overall survival of an organism, the cellular and molecular basis of olfactory critical periods have not garnered extensive study compared to visual critical periods. Recent work providing a comprehensive mapping of the highly organized olfactory neuropil and its development has in turn attracted a growing interest in how these circuits undergo plasticity during critical periods. Here, we perform a comparative review of olfactory critical periods in fruit flies and mice to provide novel insight into the importance of early odor exposure in shaping neural circuits and highlighting mechanisms found across sensory modalities.

Determination of 35 antibiotics and four β-receptor agonists in teenagers and analysis of exposure status

Antibiotics are mainly used for disease treatment and prevention, and β-receptor agonists are mainly used in the clinical treatment of respiratory diseases. Both types of drugs are also widely used in animal husbandry and aquaculture to promote animal growth and prevent disease. These drugs enter the human body through many routes and cause harm to human health. Teenagers are in a critical period of growth and development, and long-term antibiotic exposure may have adverse effects on their bodies. In this study, 442 teenagers aged 11-15 years were recruited from a middle school to investigate the body burden of various antibiotics and β-receptor agonists. The seven categories of antibiotics, including five macrolides, four tetracyclines, 10 quinolones, 11 sulfonamides, three β-lactams, one quinoxaline, and one lincosamide, and four β-receptor agonists were determined by isotope dilution and solid phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry. Analyte levels were corrected using urine creatinine, and detection rates were used for data analysis. Pearson's chi-squared test was used to analyze the correlations between detection rate and gender, age, or body mass index (BMI). Logistic regression was used to evaluate the correlation between detection rate and different groups after adjusting for confounding factors. The results showed that 397 teenagers had at least one antibiotic or β-receptor agonist in their urine, with a total detection rate of 89.8%. A total of 29 antibiotics and β-receptor agonists were detected, and the detection rate of each compound ranged from 0.2% to 59.0%. Doxycycline, oxytetracycline, and azithromycin were the top three drugs with the highest detection rates (59.0%, 56.1%, and 34.6%, respectively). Tetracyclines and macrolides were the two antibiotic categories detected most often, with detection rates of 81.9% and 42.3%, respectively. Among the antibiotics investigated, preferred veterinary antibiotics (PVAs) had the highest detection rate (85.1%), followed by human antibiotics (HAs) (41.0%). The overall detection rate of β-receptor agonists was 2.7%. Statistical analysis showed that the male was prone to be exposed to tetracycline antibiotics (odds ratio (OR)=2.17). The detection rates of macrolides differed among the different age groups and were higher in those aged 12-13 years than in those aged 11 years. As the BMI of the teenagers increased, the detection rate of macrolides gradually increased. After adjusting for age and gender, teenagers with obesity were found to be 2.35 times more likely to be exposed to macrolides than those with a normal weight. The findings suggest that teenagers are generally exposed to low levels of antibiotics, that food and the environment may be the main sources of antibiotic exposure in teenagers, and that macrolide exposure may be associated with adolescent obesity.

Activity-dependent formation of the topographic map and the critical period in the development of mammalian olfactory system.

Neural activity influences every aspect of nervous system development. In olfactory systems, sensory neurons expressing the same odorant receptor project their axons to stereotypically positioned glomeruli, forming a spatial map of odorant receptors in the olfactory bulb. As individual odors activate unique combinations of glomeruli, this map forms the basis for encoding olfactory information. The establishment of this stereotypical olfactory map requires coordinated regulation of axon guidance molecules instructed by spontaneous activity. Recent studies show that sensory experiences also modify innervation patterns in the olfactory bulb, especially during a critical period of the olfactory system development. This review examines evidence in the field to suggest potential mechanisms by which various aspects of neural activity regulate axon targeting. We also discuss the precise functions served by neural plasticity during the critical period.

Defining the roles of local precipitation and anthropogenic water sources in driving the abundance of Aedes aegypti, an emerging disease vector in urban, arid landscapes

Understanding drivers of disease vectors’ population dynamics is a pressing challenge. For short-lived organisms like mosquitoes, landscape-scale models must account for their highly local and rapid life cycles. Aedes aegypti, a vector of multiple emerging diseases, has become abundant in desert population centers where water from precipitation could be a limiting factor. To explain this apparent paradox, we examined Ae. aegypti abundances at > 660 trapping locations per year for 3 years in the urbanized Maricopa County (metropolitan Phoenix), Arizona, USA. We created daily precipitation layers from weather station data using a kriging algorithm, and connected localized daily precipitation to numbers of mosquitoes trapped at each location on subsequent days. Precipitation events occurring in either of two critical developmental periods for mosquitoes were correlated to suppressed subsequent adult female presence and abundance. LASSO models supported these analyses for female presence but not abundance. Precipitation may explain 72% of Ae. aegypti presence and 90% of abundance, with anthropogenic water sources supporting mosquitoes during long, precipitation-free periods. The method of using kriging and weather station data may be generally applicable to the study of various ecological processes and patterns, and lead to insights into microclimates associated with a variety of organisms’ life cycles.

Schizophrenia endothelial cells exhibit higher permeability and altered angiogenesis patterns in patient-derived organoids

Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterized by the manifestation of psychiatric symptoms in early adulthood. While many research avenues into the origins of SCZ during brain development have been explored, the contribution of endothelial/vascular dysfunction to the disease remains largely elusive. To model the neuropathology of SCZ during early critical periods of brain development, we utilized patient-derived induced pluripotent stem cells (iPSCs) to generate 3D cerebral organoids and define cell-specific signatures of disease. Single-cell RNA sequencing revealed that while SCZ organoids were similar in their macromolecular diversity to organoids generated from healthy controls (CTRL), SCZ organoids exhibited a higher percentage of endothelial cells when normalized to total cell numbers. Additionally, when compared to CTRL, differential gene expression analysis revealed a significant enrichment in genes that function in vessel formation, vascular regulation, and inflammatory response in SCZ endothelial cells. In line with these findings, data from 23 donors demonstrated that PECAM1+ microvascular vessel-like structures were increased in length and number in SCZ organoids in comparison to CTRL organoids. Furthermore, we report that patient-derived endothelial cells displayed higher paracellular permeability, implicating elevated vascular activity. Collectively, our data identified altered gene expression patterns, vessel-like structural changes, and enhanced permeability of endothelial cells in patient-derived models of SCZ. Hence, brain microvascular cells could play a role in the etiology of SCZ by modulating the permeability of the developing blood brain barrier (BBB).

An enriched environment ameliorates the reduction of parvalbumin-positive interneurons in the medial prefrontal cortex caused by maternal separation early in life.

Early child maltreatment, such as child abuse and neglect, is well known to affect the development of social skills. However, the mechanisms by which such an adverse environment interrupts the development of social skills remain unelucidated. Identifying the period and brain regions that are susceptible to adverse environments can lead to appropriate developmental care later in life. We recently reported an excitatory/inhibitory imbalance and low activity during social behavior in the medial prefrontal cortex (mPFC) of the maternal separation (MS) animal model of early life neglect after maturation. Based on these results, in the present study, we investigated how MS disturbs factors related to excitatory and inhibitory neurons in the mPFC until the critical period of mPFC development. Additionally, we evaluated whether the effects of MS could be recovered in an enriched environment after MS exposure. Rat pups were separated from their dams on postnatal days (PDs) 2-20 (twice daily, 3 h each) and compared with the mother-reared control (MRC) group. Gene expression analysis revealed that various factors related to excitatory and inhibitory neurons were transiently disturbed in the mPFC during MS. A similar tendency was found in the sensory cortex; however, decreased parvalbumin (PV) expression persisted until PD 35 only in the mPFC. Moreover, the number of PV+ interneurons decreased in the ventromedial prefrontal cortex (vmPFC) on PD 35 in the MS group. Additionally, perineural net formation surrounding PV+ interneurons, which is an indicator of maturity and critical period closure, was unchanged, indicating that the decreased PV+ interneurons were not simply attributable to developmental delay. This reduction of PV+ interneurons improved to the level observed in the MRC group by the enriched environment from PD 21 after the MS period. These results suggest that an early adverse environment disturbs the development of the mPFC but that these abnormalities allow room for recovery depending on the subsequent environment. Considering that PV+ interneurons in the mPFC play an important role in social skills such as empathy, an early rearing environment is likely a very important factor in the subsequent acquisition of social skills.

Avian extraembryonic membranes respond to yolk corticosterone early in development.

During times of maternal stress, developing embryos can be exposed to elevated levels of glucocorticoids, which can affect development and permanently alter offspring phenotype. In placental species, the placenta mediates fetal exposure to maternal glucocorticoids via metabolism, yet the placenta itself responds to glucocorticoids to regulate offspring growth and development. In oviparous species, maternal glucocorticoids can be deposited into the egg yolk and are metabolized early in development. This metabolism is mediated by the extraembryonic membranes, but it is unknown if the extraembryonic membranes also respond to maternal glucocorticoids in a way comparable to the placenta. In this study, we quantified the expression of acyl-CoA thioesterase 13 (Acot13) as an initial marker of the membrane's response to corticosterone in chicken (Gallus gallus) eggs. Acot13 regulates fatty acid processing in the embryo, to potentially regulate resource availability during development. We addressed the following questions using Acot13 expression: 1) Do the extraembryonic membranes respond to yolk corticosterone early in development? 2) Is the response to corticosterone dependent on the dose of corticosterone? 3) What is the duration of the response to corticosterone? 4) Does a metabolite of corticosterone (5β-corticosterone) elicit the same response as corticosterone? We found that corticosterone significantly induces the expression of Acot13 on day four of development and that expression of Acot13 increases with the dose of corticosterone. Further, we found expression of Acot13 is significantly elevated by corticosterone on days four and six of development compared to oil treated eggs, but not on days eight and ten. Although this response is transient, it occurs during a critical period of development and could initiate a cascade of events that ultimately alter offspring phenotype. Finally, we found that 5β-corticosterone does not increase the expression of Acot13, indicating that metabolism inactivates corticosterone. Ultimately, this study provides insight into the mechanisms underlying how maternally deposited glucocorticoids can affect embryonic development.

The impact of menarche on hippocampal mechanisms of severity of psychotic-like experiences in the ABCD study

Accumulating evidence suggests that estrogens play an important modulatory role in the pathogenesis of psychosis. Estrogens come online within a dynamic developmental context of emerging psychopathology and neurodevelopment. As a result, estradiol (the primary form of estrogen) may influence psychosis lability directly or indirectly through its neurodevelopmental influence on estrogens-sensitive areas like the hippocampus. Understanding this influence may provide novel insight into mechanisms of psychosis lability. This study included baseline and year 2 timepoints from 4422 female participants from the Adolescent Brain Cognitive Development (ABCD) study (age 8–13), who varied in estradiol availability (pre-menarche, post-menarche, pre- and post-menarche timepoints). Estradiol availability was related to psychotic-like experiences (PLE) severity both directly and as an interactive effect with hippocampal connectivity using menarche status (pre/post) in a multilevel model. PLE severity was highest in individuals with early menarche emphasizing the importance of the developmental timing. Although PLE severity decreased over time in the sample, it stayed clinically-relevant over 2 years. Lower hippocampal connectivity was related to elevated PLE severity. This effect was moderated by estradiol; before the availability of estradiol (pre-menarche), lower hippocampal connectivity significantly contributed to the PLE severity, but when estradiol was available (post-menarche) hippocampal dysconnectivity did not account for PLE severity. This moderation suggests that the estrodiol’s influence on hippocampal plasticity also reduced the mechanistic role of the hippocampus on PLE severity. Further, the lack of a significant direct reduction of PLE severity post-menarche, may suggest an increased role for other interacting psychosis lability factors during this critical developmental period.