Critical Developmental Period Research Articles

Impact of a philosophical intervention on the reduction of depression in high school students.

Adolescence is a critical and challenging period in development; therefore, it is of utmost importance to address and prevent disorders such as depression or anxiety. The present study aimed to evaluate the effect of a philosophical intervention on depression rates in high school students. The method consisted of the evaluation of depression before and after the intervention with the BDI-Y test. Of the cases of the young people attended in the intervention workshops, on average, their depressive classification decreased by 67%. The implementation of the workshops with content in ethical values can be a model of early mental health intervention to reduce the levels of depression in high school students, which created a multiplier effect in the class groups, as well as in the increase of coexistence and teamwork.

Programmatic and Legal Preparedness of India on Early Childhood Development

Abstract Early childhood development (ECD) is the period of rapid and critical development that occurs from conception upto 6 to 8 years of age. During this time, children experience significant growth and changes in all areas of development, including physical, cognitive, linguistic and socio - emotional. A variety of factors can influence ECD, including genetics, environment and health. This presents a unique opportunity to invest in ECD and build a foundation for a prosperous and equitable future for the country. This review looked at the programmatic and legal preparedness of India in taking forward the agenda of ECD. A review of the laws and programs was undertaken to discern this objective. Besides desk review, interviews were conducted with programme officers handling child health at the central and state levels. Based on the direction for action given by the national health and other policies and several statutes, the central government has launched various programmes and schemes under various ministries within the overarching framework provided by the Constitution of India. There are 5 policies, 15 statutes/acts/laws and nearly 40 government schemes and programmes relating to children in India. The activities are majorly coordinated through Ministries of Woman and Child Development, Health and Family Welfare, Ministry of Education, Drinking Water and Sanitation and Tribal Affairs. Despite these efforts, there is still a significant gap between the demand and supply for ECD services.

Psychosocial Comorbidities in patients with pediatric alopecia areata: A Literature Review.

Alopecia areata (AA), a chronic autoimmune disorder causing non-scarring hair loss, has a greater prevalence in the pediatric population. Like many visible dermatologic disorders, AA can cause significant psychosocial impairment, particularly in children who are undergoing critical periods of psychosocial development. This paper investigates the psychosocial impact of AA on children. A systematic review was conducted using PRISMA guidelines. SCOPUS and PubMed databases were utilized with the terms "alopecia areata," "pediatric," and "psychosocial comorbidities." 12 articles were reviewed, with 6 meeting inclusion criteria for detailed analysis. The review revealed prominent associations between AA and psychosocial comorbidities in children. Psychiatric conditions including anxiety, depression, and OCD, were prevalent in pediatric AA patients, with exacerbation due to increased disease severity. These negatively impacted the Quality of Life (QoL) in affected children. Additionally, the comorbidities extended beyond psychiatric diagnoses, impacting self-esteem, academic performance, peer relationships, and body image satisfaction in children. This literature review highlights the significant impact of various psychosocial comorbidities in children with AA, emphasizing the need for early identification and intervention. Healthcare professionals, including psychiatrists, therapists, and dermatologists, can play a significant role in treating pediatric patients with AA. Dermatologists can play a critical role in diagnosing AA and identifying psychosocial comorbidities that may arise and refer patients to appropriate care. Future research should focus on elucidating effective screening tools for dermatologists to identify these comorbidities early, ultimately improving the overall well-being of children with AA.

Towards personalized precision functional mapping in infancy

Abstract The precise network topology of functional brain systems is highly specific to individuals and undergoes dramatic changes during critical periods of development. Large amounts of high-quality resting state data are required to investigate these individual differences, but are difficult to obtain in early infancy. Using the template matching method, we generated a set of infant network templates to use as priors for individualized functional resting-state network mapping in two independent neonatal datasets with extended acquisition of resting-state functional MRI (fMRI) data. We show that template matching detects all major adult resting-state networks in individual infants and that the topology of these resting-state network maps is individual-specific. Interestingly, there was no plateau in within-subject network map similarity with up to 25 minutes of resting-state data, suggesting that the amount and/or quality of infant data required to achieve stable or high-precision network maps is higher than adults. These findings are a critical step towards personalized precision functional brain mapping in infants, which opens new avenues for clinical applicability of resting-state fMRI and potential for robust prediction of how early functional connectivity patterns relate to subsequent behavioral phenotypes and health outcomes.

Sex differences during development in cortical temporal processing and event related potentials in wild-type and fragile X syndrome model mice

BackgroundAutism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD.MethodsTo fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice.ResultsThe results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes.ConclusionsThese results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

Kids+ Parent Infant Program (PIP): a community model for supporting partnerships in early developmental follow-up and support.

High-risk infants are discharged home from hospital with increased care needs and the potential for the emergence of developmental disabilities, contributing to high levels of parental stress and anxiety. To enable optimal outcomes for high-risk infants and their families, developmental follow-up programs need to continue following hospital discharge. However, current follow-up care for high-risk infants is variable in terms of type, access and equity, and there seems to be a gap in existing services such as supporting the transition home, parental support, and inclusion of all at-risk infants regardless of causality. Routine follow-up that identifies developmental delays or neuromotor concerns can facilitate timely referral and access to targeted intervention during critical periods of development. The Kids+ Parent Infant Program (PIP) is a unique model of developmental follow-up that shares some characteristics with established programs, but also includes additional key elements for a seamless, wrap-around service for all high-risk infants and their families living in a regional area of Australia. This community-based program provides integrated assessment and intervention of infants, alongside parent support and education, embracing a holistic model that accounts for the complexity and interrelatedness of infant, parent, medical and developmental factors. By prioritising the well-being of high-risk infants and their families, the Kids+ PIP paves the way for improved developmental outcomes and provides an innovative model for developmental follow-up, with the potential for reproduction in other healthcare settings.

Parvalbumin interneurons in human ventromedial prefrontal cortex: a comprehensive post-mortem study of myelination and perineuronal nets in neurotypical individuals and depressed suicides with and without a history of child abuse.

Cortical parvalbumin interneurons (PV+) are major regulators of excitatory/inhibitory information processing, and their maturation is associated with the opening of developmental critical periods (CP). Recent studies reveal that cortical PV+ axons are myelinated, and that myelination along with perineuronal net (PNN) maturation around PV+ cells is associated with the closures of CP. Although PV+ interneurons are susceptible to early-life stress, their relationship between their myelination and PNN coverage remains unexplored. This study compared the fine features of PV+ interneurons in well-characterized human post-mortem ventromedial prefrontal cortex samples (n = 31) from depressed suicides with or without a history of child abuse (CA) and matched controls. In healthy controls, 81% of all sampled PV+ interneurons displayed a myelinated axon, while a subset (66%) of these cells also displayed a PNN, proposing a relationship between both attributes. Intriguingly, a 3-fold increase in the proportion of unmyelinated PV+ interneurons with a PNN was observed in CA victims, along with greater PV-immunofluorescence intensity in myelinated PV+ cells with a PNN. This study, which is the first to provide normative data on myelination and PNNs around PV+ interneurons in human neocortex, sheds further light on the cellular and molecular consequences of early-life adversity on cortical PV+ interneurons.

The carryover effects of embryonic incubation temperature on subsequent growth and thermal tolerance in white sturgeon

Environmental variation experienced during early periods of development can lead to persistent phenotypic alteration, known as carryover effects. Such effects increase concern for threatened or endangered species such as the white sturgeon (Acipenser transmontanus), particularly considering expected thermal changes due to climate change. We evaluated how temperature during embryonic development affects physiological parameters such as larval and early juvenile growth and thermal tolerance. Nechako River white sturgeon embryos were incubated at different environmental temperatures (Te) of 12°C (the natural spawning temperature of this population), 15°C (the hatchery incubation temperature), and 18 °C (representing potential increases in river temperatures given global climate change). After hatch, fish were reared at a common 15 °C for 80 days post-hatch (dph). Individuals from each temperature treatment were tested for thermal tolerance using the critical thermal maximum method (CTmax), euthanized, and measured. Fish were examined at regular intervals from 13 to 80 dph, which bridged the time from the start of exogenous feeding through the transition into early juveniles. We found carryover effects of high embryonic Te in the short term for both thermal tolerance and growth. Fish that developed at 18 °C had the lowest thermal tolerance during the start of exogenous feeding. However, differences in thermal tolerance were small for early juveniles and were unlikely to be ecologically relevant in the longer term. Fish that developed at 18 °C were smallest over the observation period, indicating a possible cost for survival from increasing environmental temperatures during embryonic development. This research represents a window into a critical period of development during which fish are particularly vulnerable to climatic variation, and shows that cooler temperatures (12°C ) during incubation are optimal for this population. The results can inform environmental managers on the best strategies to help conserve current white sturgeon populations across their range.

Loss of Htr1B Leads to a Failure in the Neonate Autoresuscitation Reflex

Sudden Infant Death Syndrome (SIDS) is the leading cause of death in infants under the age of 1, with an unknown etiology, that takes the lives of 3,400 infants per year in the US alone. Interestingly, SIDS cases show males predominance (60%), however this sexual disparity in is not fully understood. SIDS is believed to follow a triple risk hypothesis model where the infant has an innate vulnerability, is at a critical developmental period, and is challenged with an exogenous stressor. A leading hypothesis indicates many SIDS cases are mechanistically driven by a failure in the autoresuscitation reflex. The autoresuscitation reflex is a series of gasps that occur to revitalize normal cardiorespiratory function when an infant falls into a hypoxic coma, characterized by an apnea and bradycardia, due to severe hypoxic conditions (i.e., rebreathing while sleeping in face down or with the face blocked). Although the cause of failure in the autoresuscitation reflex for SIDS remains unknown, post-mortem studies have found abnormalities related to the central serotonin (5-HT) neurotransmitter system, including several 5-HT receptors (5-HTr’s). Follow up studies in animal models show that 5-HT system perturbations result in a significant survival decrease in neonatal animals during anoxic (3% CO2/balance N2) gas challenges that test the autoresuscitation function, including pharmacological receptor manipulations. Furthermore, adult animal studies report that 5-HT receptor stimulation alters various respiratory parameters (i.e., tidal volume, respiratory rate, gasping). What remains to be understood is the cellular and molecular mechanisms through which 5-HT plays a role in the autoresuscitation reflex and how those mechanism may be disrupted in SIDS. We hypothesize that Htr1B is required for successful autoresuscitation. To test this hypothesis, we utilized an automated closed loop robotic platform for neonate cardio-respiratory measurements ( Looper) to assay P7 Htr1B loss of function mice for their abilities to survive repeated anoxic gas challenges testing the autoresuscitation reflex. Using Looper, we find that the loss of Htr1B decreases survival to repeated anoxic challenges compared to wild type (WT) controls in both male and female mice. Additionally, a subset of male heterozygous Htr1B mice survive fewer challenges compared to WT mice, whereas others survive a similar number of challenges as WT mice; a phenotype not observed in female mice. Our data supports the hypothesis that modulations to the serotonin system via Htr1B is important in eliciting the autoresuscitation response. Future studies aim to investigate additional respiratory parameters from respiratory trace data, in addition to recovery parameters, and functionally mapping out where in the brainstem and what neuronal populations require the expression of this receptor for the autoresuscitation reflex. R01 HL161142. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Butyrylcholinesterase Is Not Required for the Neonatal Autoresuscitation Reflex

Sudden Infant Death Syndrome (SIDS) is the leading cause of infant death under the age of one year of age, taking the lives of more than 1,400 infants annually, and comprising approximately 41% of all Sudden Unexpected Infant Death (SUID) cases. SIDS etiology remains vastly unknown but is best explained via a triple risk model that proposes SIDS occurs in a vulnerable infant during a critical developmental period when triggered by an external stressor. In SIDS it is hypothesized that there is first a failure in arousal followed by failure in the protective autoresuscitation reflex; a defense mechanism for an infant that is in a hypoxic coma, that promotes deep gasping to attempt to restart cardiovascular function. Many SIDS case studies reveal associations with genetic variants and abnormal biomarkers; however, it is unclear whether these variants are causal. Recently a case study identified a broad association between reduced blood BChE activity and SIDS cases, yet the functional relationship between BChE and respiratory regulation remains to be investigated. We aimed to functionally test the relationship between BChE and the neonatal autoresuscitation reflex utilizing a rapid pipeline for precision genetic modeling and high-throughput functional testing developed by the Ray Lab. BChE loss of function mice, generated through targeted genetic editing, were tested for neonatal autoresuscitation on our automated closed loop phenotyping platform, Looper. Postnatal day 7-8 mice were exposed to 3% CO2 and 97% N2 stimuli to induce a state of hypoxia resulting in detection of bradycardia, initial hyperventilation, hypoventilation, and apnea followed by restoration of room air conditions to facilitate the autoresuscitation reflex and cardio-respiratory recovery. Male and female mice were exposed to repeated anoxic gas challenges and allowed to autoresuscitate until death occurred. Data suggest that loss of BChE function does not affect neonatal autoresuscitation. BChE knockout mice and heterozygous mice survived similar amounts of anoxic challenges as wild type controls. No sex differences were observed between the number of anoxic challenges survived in males and females for all genotypes. Our data demonstrate the first functional assessment of BChE in neonatal cardio-respiratory regulation and the autoresuscitation response and highlight that BChE is not required for successful neonatal autoresuscitation. Additional analyses of respiratory parameters from respiratory trace data for BChE loss of function mice will aid in a further understanding if BChE loss of function is implicated in other aspects respiratory regulation. Funding: Precision Core funding U54 OD030165. NIH/NHLBI R01HLN161142-01 and R01HL130249-07. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Deciduous teeth from the New Hampshire Birth Cohort Study: Early life environmental and dietary predictors of dentin elements

BackgroundSparse research exists on predictors of element concentrations measured in deciduous teeth. ObjectiveTo estimate associations between maternal/child characteristics, elements measured in home tap water during pregnancy and element concentrations in the dentin of shed deciduous teeth. MethodsOur analysis included 152 pregnant person-infant dyads followed from the second trimester through the end of the first postnatal year from the New Hampshire Birth Cohort Study. During pregnancy and early infancy, we collected dietary and sociodemographic information via surveys, measured elements in home tap water, and later collected naturally exfoliated teeth from child participants. We measured longitudinal deposition of elements in dentin using LA-ICP-MS. Multivariable linear mixed models were used to estimate associations between predictors and dentin element concentrations. ResultsWe measured 12 elements in dentin including those previously reported (Ba, Mn, Pb, Sr, Zn) and less frequently reported (Al, As, Cd, Cu, Hg, Li, and W). A doubling of Pb or Sr concentrations in water was associated with higher dentin Pb or Sr respectively in prenatally formed [9% (95%CI: 3%, 15%); 3% (1%, 6%)] and postnatally formed [10% (2%, 19%); 6% (2%, 10%)] dentin. Formula feeding from birth to 6 weeks or 6 weeks to 4 months was associated with higher element concentrations in postnatal dentin within the given time period as compared to exclusive human milk feeding: Sr: 6 weeks: 61% (36%, 90%) and 4 months: 85% (54%, 121%); Ba: 6 weeks: 35% (3.3%, 77%) and 4 months: 42% (10%, 83%); and Li: 6 weeks: 61% (33%, 95%) and 4 months: 58% (31%, 90%). SignificanceThese findings offer insights into predictors of dentin elements and potential confounders in exposure-health outcome relationships during critical developmental periods.

Title: Supporting Adolescent Well-being at School: Integrating Transformative Social and Emotional Learning and Trauma-Informed Education

There is an urgent need to support the social and emotional well-being of adolescents with experiences of adversity and trauma. Adolescence is a critical period of development for promoting social and emotional competencies, which can prevent poor mental health and problematic substance use and promote thriving during challenging teenage years and beyond. Both transformative social and emotional learning (TSEL) and trauma-informed programs for schools (TIPS) have been identified as promising practices for supporting social and emotional well-being among young people with experiences of adversity. We propose a pragmatic theory of action for schools for implementing and evaluating initiatives that integrate TSEL and TIPS made up of three iterative components: awareness, assessment, and action. The TSEL +TIPS Theory of Action is illustrated by a case study of a cross-sectoral collaboration of government schools, researchers, healthcare, and adolescents to implement TSEL and TIPS initiatives in British Columbia, Canada. The case study provides evidence forthe feasibility of TSEL + TIPS Theory of Action and may serve as an example for other regions as experiences of adversity and poor mental health continue to rise among adolescents globally.

Impact of Prenatal LPS and Early-life Constant Light Exposure on Circadian Gene Expression Profiles in Various Rat Tissues

Exposure to lipopolysaccharide (LPS) during prenatal development leads to various changes in neurobiological and behavioural patterns. Similarly, continuous exposure to constant light (LL) during the critical developmental period of the circadian system affects gene expression in various tissues in adulthood. Given the reciprocal nature of the interaction between the circadian and the immune systems, our study primarily investigated the individual effects of both interventions and, more importantly, their combined effect. We aimed to explore whether there might be a potential synergistic effect on circadian rhythms and their parameters, focussing on the expression of clock genes, immune-related genes, and specific genes in the hippocampus, pineal gland, spleen and adrenal gland of rats at postnatal day 30. Our results show a significant influence of prenatal LPS and postnatal LL on the expression profiles of all genes assessed. However, the combination of prenatal LPS and postnatal LL only revealed an enhanced negative effect in a minority of the comparisons. In most cases, it appeared to attenuate the changes induced by the individual interventions, restoring the measured parameters to values closer to those of the control group. In particular, genes such as Nr1d1, Aanat and Tph1 showed increased amplitude in the pineal gland and spleen, while the kynurenine enzymes Kynu and KatII developed circadian rhythmicity in the adrenal glands only after the combined interventions. Our data suggest that a mild immunological challenge during prenatal development may play a critical role in triggering an adaptive response of the circadian clock later in life.

Interactions between intestinal microbiota and metabolites in zebrafish larvae exposed to polystyrene nanoplastics: Implications for intestinal health and glycolipid metabolism

Previous studies have shown the harmful effects of nanoscale particles on the intestinal tracts of organisms. However, the specific mechanisms remain unclear. Our present study focused on examining the uptake and distribution of polystyrene nanoplastics (PS-NPs) in zebrafish larvae, as well as its toxic effects on the intestine. It was found that PS-NPs, marked with red fluorescence, primarily accumulated in the intestine section. Subsequently, zebrafish larvae were exposed to normal PS-NPs (0.2–25 mg/L) over a critical 10-day period for intestinal development. Histopathological analysis demonstrated that PS-NPs caused structural changes in the intestine, resulting in inflammation and oxidative stress. Additionally, PS-NPs disrupted the composition of the intestinal microbiota, leading to alterations in the abundance of bacterial genera such as Pseudomonas and Aeromonas, which are associated with intestinal inflammation. Metabolomics analysis showed alterations in metabolites that are primarily involved in glycolipid metabolism. Furthermore, MetOrigin analysis showed a significant correlation between bacterial flora (Pedobacter and Bacillus) and metabolites (D-Glycerate 2-phosphate and D-Glyceraldehyde 3-phosphate), which are related to the glycolysis/gluconeogenesis pathways. These findings were further validated through alterations in multiple biomarkers at various levels. Collectively, our data suggest that PS-NPs may impair the intestinal health, disrupt the intestinal microbiota, and subsequently cause metabolic disorders.

An Exploration of Swedish Adolescents’ Experiences of Mobile Apps for Physical Activity

Recent reports on children and adolescents’ physical activity indicate that approximately 80% do not meet the World Health Organisation’s recommended levels of physical activity. Childhood is a critical period of development; as such, it is important to prioritize health promotion in this phase of one’s life. Use of gamification in mobile apps has been shown to positively influence physical activity levels in children and adolescents. Inclusion of behaviour change techniques (BCTs) has been noted to increase the effect of health promoting interventions. Previous research highlights that children and adolescents find the BCTs of goal setting/planning, feedback, reward, self-monitoring, social comparison, and social support to be of interest. The aim of this study was to explore Swedish adolescents’ experience with physical activity and apps with a focus on the influence of BCTs. Three focus group interviews were undertaken with a total of 18 participants (11-15 years of age). The data were explored using reflective thematic analysis. In addition to the BCTs identified in previous research, participants in the present study indicated they were positive about mobile apps providing instruction on how to perform a behaviour, demonstration of the behaviour, and the influence of removal of reward. Other attractive features of physical activities apps included developing a streak, competition, and provision of an adequate level of challenge. The present study contributes to a deeper understanding of how BCTs and other features can be implemented in physical activity apps, where individualization and renewal appear to be more important than the actual content features. These findings are important for future work to create interventions that increase the level of physical activity among adolescents both in Sweden and other countries.

Describing the geographical linkage between the UK Millennium Cohort Study and crime incidents in England and Wales

BackgroundEnhancing longitudinal cohort studies by linking routine external data to them is increasingly used to evaluate how local environments impact participants' outcomes (e.g. crime on adolescents' perception of security and victimisation). ObjectiveTo describe the geographical linkage between the UK Millennium Cohort Study (MCS) and street-level crime incidents reported to the Police in England and Wales, and to estimate crime count and rates around MCS participants' residences. MethodsEight years of monthly street-level police data were linked to the residential postcodes of MCS participants living in England and Wales in surveys 5, 6 and 7 to create individual-level variables of neighbourhood crime counts and rates (28,724 surveys and 11,365 individuals). Radial buffers around participants' residences were created at ages 11, 14 and 17. Crime counts and rates were created prior to the month of interview (at 1, 3, 6, 9, and 12 months prior). A homogenisation of crime categories reported in the police data was conducted to evaluate changes over time and areas. Multivariate models were used to study the association between MCS participants' demographic characteristics and derived measures of neighbourhood crime. ResultsWhile total crime rates and counts around MCS participants remain stable over the period, they hide heterogeneous upward and downward trends in specific sub-categories, with violence and sexual offences showing a larger increase. We observe a negative socioeconomic gradient between household income deciles, recorded at age 11, and subsequent exposure to neighbourhood crime. ConclusionLinking routine crime data to longitudinal studies, such as the MCS, which follow children and their families through a critical period of development, can provide a new resource to understand how local crime impacts child and adolescent outcomes.

Viral-mediated inflammation by Poly I:C induces the chemokine CCL5 in NK cells and its receptors CCR1 and CCR5 in microglia in the neonatal rat cerebellum

Abstract Objectives To study the effect of viral inflammation induced by Polyinosinic:polycytidylic acid (PIC) on the cerebellum during a critical period of development in rats. Methods Neonatal rat pups were treated with PIC on postnatal days (PN) 8 and 10 after which we quantified RNA using Nanostring, qRT-PCR and RNAscope and analyzed immune cells through flow cytometry and immunohistochemistry on PN11. Using the same paradigm, we also analyzed play juvenile behavior, anxiety-like behavior, motor balance using the balance beam and the rotarod assays as well as fine motor behavior using the sunflower seed opening test. Results We determined that male and female pups treated with PIC reacted with a significant increase in CCL5, a chemotactic cytokine that attracts T-cells, eosinophils and basophils to the site of inflammation, at PN11. PIC treatment also increased the expression of two receptors for CCL5, CCR1 and CCR5 in the cerebellar vermis in both males and females at PN11. In-situ hybridization (RNAscope®) for specific transcripts revealed that microglia express both CCL5 receptors under inflammatory and non-inflammatory conditions in both males and females. PIC treatment also increased the total number of CCL5+ cells in the developing cerebellum which were determined to be both natural killer cells and T-cells. There were modest but significant impacts of PIC treatment on large and fine motor skills and juvenile play behavior. Conclusions Our findings suggest an important role for CCL5 and other immune cells in mediating inflammation in the developing cerebellum that potentially impact the maturation of cerebellar neurons during a critical period of development.

Correlation of gestational age and age at death in sudden infant death syndrome: another pointer to the role of critical developmental period?

Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications. We did a detailed analysis of CDC data spanning over two decades (1983-2011). We focused not only on the correlation between two age variables (gestational and age at death), but also on the possibility of misdiagnosis. Also, we attempted to account for potential biases in the data induced by the ICD-9/ICD-190 transition or the "Back to Sleep" campaign. The peak of deaths in the third month of life, that was the main argument for the role of the critical development period, wasn't unique to SIDS. However, we confirmed an almost linear and negative correlation between gestational age and the week of death due to SIDS. This pattern (slope of correlation < 0 and significance of correlation p < 0.05) is characteristic of SIDS among all diseases analyzed in the study. We interpret the results as the evidence of the role of the critical development period in SIDS etiology. Possibly more attention in the future research should be put to theories that are based on homeostatic control.

Prolonged use of a soft diet during early growth and development alters feeding behavior and chewing kinematics in a young animal model.

In infants and children with feeding and swallowing issues, modifying solid foods to form a liquid or puree is used to ensure adequate growth and nutrition. However, the behavioral and neurophysiological effects of prolonged use of this intervention during critical periods of postnatal oral skill development have not been systematically examined, although substantial anecdotal evidence suggests that it negatively impacts downstream feeding motor and coordination skills, possibly due to immature sensorimotor development. Using an established animal model for infant and juvenile feeding physiology, we leverage X-ray reconstruction of moving morphology to compare feeding behavior and kinematics between 12-week-old pigs reared on solid chow (control) and an age- and sex-matched cohort raised on the same chow softened to a liquid. When feeding on two novel foods, almond and apple, maintenance on a soft diet decreases gape cycle duration, resulting in a higher chewing frequency. When feeding on almonds, pigs in this group spent less time ingesting foods compared to controls, and chewing cycles were characterized by less jaw rotation about a dorsoventral axis (yaw) necessary for food reduction. There was also a reduced tendency to alternate chewing side with every chew during almond chewing, a behavioral pattern typical of pigs. These more pronounced impacts on behavior and kinematics during feeding on almonds, a tougher and stiffer food than apples, suggest that food properties mediate the behavioral and physiological impacts of early texture modificationand that the ability to adapt to different food properties may be underdeveloped. In contrast, the limited effects of food texture modification on apple chewing indicate that such intervention/treatment does not alter feeding behavior of less challenging foods. Observed differences cannot be attributed to morphology because texture modification over the treatment period had limited impact on craniodental growth. Short-term impacts of soft-texture modification during postweaning development on feeding dynamics should be considered as potential negative outcomes of this treatment strategy.

Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.

α-Klotho (α-Kl) is a modulator of aging, neuroprotection, and cognition. Transcription of the Klotho gene produces two splice variants-a membrane protein (mKl), which can be cleaved and released into the extracellular milieu, and a truncated secreted form (sKl). Despite mounting evidence supporting a role for α-Kl in brain function, the specific roles of α-Kl isoforms in neuronal development remain elusive. Here, we examined α-Kl protein levels in rat brain and observed region-specific expression in the adult that differs between isoforms. In the developing hippocampus, levels of isoforms decrease after the third postnatal week, marking the end of the critical period for development. We overexpressed α-Kl isoforms in primary cultures of rat cortical neurons and evaluated effects on brain-derived neurotrophic factor (BDNF) signaling. Overexpression of either isoform attenuated BDNF-mediated signaling and reduced intracellular Ca2+ levels, with mKl promoting a greater effect. mKl or sKl overexpression in hippocampal neurons resulted in a partially overlapping reduction in secondary dendrite branching. Moreover, mKl overexpression increased primary dendrite number. BDNF treatment of neurons overexpressing sKl resulted in a dendrite branching phenotype similar to control neurons. In neurons overexpressing mKl, BDNF treatment restored branching of secondary and higher order dendrites close, but not distal, to the soma. Taken together, the data presented support the idea that sKl and mKl play distinct roles in neuronal development, and specifically, in dendrite morphogenesis.