Rapid Brain Development Research Articles

Repeated high-dose esketamine in early postnatal rats leads to behavioural deficits with long-term modifications in white matter microstructural integrity

Esketamine is commonly used for sedation or general anaesthesia in infants and young children. However, repeated esketamine administration during periods of rapid brain growth and development may result in various pathophysiological and cognitive changes. Therefore, this study aimed to investigate the influence of recurrent esketamine exposure on long-term behavioural and white matter consequences. Seven-day-old (P7) male rats were allocated to control, high-, and low-dose groups. Behavioural paradigm assessment was conducted at P25–29. Diffusion tensor imaging revealed long-term effects on water diffusivity in the splenium and cingulum white matter of the corpus callosum at P30. Subsequent two-dimensional structure-tensor analysis of brain tissue sections stained with Luxol fast blue (LFB) showed marked changes in the white matter microstructure in rats after multiple exposures to varying esketamine doses. High-dose esketamine significantly reduced activity time and total distance in the open-field experiment. High-dose esketamine exposure might lead to impaired short-term memory in rats. Additionally, the high-dose group showed prolonged immobility time during the forced swimming test. On the balance beam, the high-dose group displayed more right turns and right-foot slips and lower time spent on the rotating bar, indicating motor defects, than did the other groups. Diffusion tensor imaging demonstrated a decreased water molecule diffusion ability in the corpus callosum in the high-dose group. LFB staining indicated microstructural differences in the white matter of animals in the high-dose group. These findings suggest that behavioural deficits in high-dose esketamine-treated rats are at least partially attributed to changes in the white matter microstructure.

IMPLEMENTASI PEMBELAJARAN HADITS MELALUI METODE GERAKAN UNTUK MENINGKATKAN HAFALAN DAN KUALITAS SDM DI DESA WIBAMULYA

Learning Hadith for children, let alone memorizing and applying it in everyday life, is very important and good for children's brain development. The rapid development of children's brain makes it easier for educators to develop aspects of their development, one of which is religious values, positive habits that children will use in their daily lives. Based on the analysis of the problems received by the author from the community in Wibawamulya Village, with the availability of the number of Qur'anic education parks with adequate infrastructure, it is still necessary to make efforts to increase the literacy of hadith education by implementing a program to improve the quality of human resources in Wibawamulya Village with hadith education using the motion method. Children lack concentration when learning hadith, feel bored and less interested in learning hadith so that memorization of hadith is not well achieved and forget the hadith that has been learned before. This causes the class to be noisy and not conducive when learning hadith takes place. Children prefer to talk to themselves when the educator is guiding their memorization. Based on the existing problems, the author uses qualitative research methods. The purpose of this community service is to understand hadith learning and can be implemented to students. The method of implementing this community service applies community education methods in the form of teaching and training. The results of the service have a positive impact in the form of increasing interest in learning hadith, memorizing hadith, and teacher creativity in learning methods.

Whole-head high-density diffuse optical tomography to map infant audio-visual responses to social and non-social stimuli

Abstract Infancy is a time of rapid brain development. High-density diffuse optical tomography (HD-DOT) is an optical neuroimaging method that maps changes in cortical haemoglobin concentration, a marker of functional brain activation. Recent years have seen a huge advance in wearable hardware for HD-DOT, however previous headgear has only been capable of sampling specific areas of the cortex. In this work, we aimed to develop headgear capable of sampling across the whole infant scalp surface and to conduct a proof-of-concept demonstration of whole-head HD-DOT in infants aged 5 to 7 months. We developed a whole-head infant implementation of the high-density LUMO design developed by Gowerlabs Ltd. (UK). HD-DOT data were collected from a cohort of infants (N = 16) during the presentation of a screen-based paradigm assessing social processing. Using whole-head HD-DOT, we mapped activity across the entirety of the optically-accessible cortex which far exceeds coverage achieved by previous infant optical neuroimaging methods. We found activity in temporal regions which corroborates previous research. Further, we mapped activity in regions outside those typically sampled in infant research using social processing paradigms, finding activation in regions across the occipital, parietal, and frontal cortices as well as an apparent inverted response in sensorimotor regions. Following this proof-of-concept, we envisage that whole-head HD-DOT will be applied to map the interaction between different regions of the brain, opening new avenues to map activity in the awake infant brain to better understand the trajectory of typical and atypical neurodevelopment.

Detailed delineation of the fetal brain in diffusion MRI via multi-task learning.

Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain inutero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain's cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.

Characterizing normal perinatal development of the human brain structural connectivity.

Early brain development is characterized by the formation of a highly organized structural connectome, which underlies brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development, inherently low signal quality, imaging difficulties, and high inter-subject variability. These factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational method based on spatio-temporal averaging in the image space for determining such baselines. We used this method to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in the perinatal stage. We observed increases in measures of network integration and segregation, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. Our proposed method also showed considerable agreement with an alternative technique based on connectome averaging. The new computational method and results of this study can be useful for assessing normal and abnormal development of the structural connectome early in life.

Microstate Analysis of Continuous Infant EEG: Tutorial and Reliability

Microstate analysis of resting-state EEG is a unique data-driven method for identifying patterns of scalp potential topographies, or microstates, that reflect stable but transient periods of synchronized neural activity evolving dynamically over time. During infancy – a critical period of rapid brain development and plasticity – microstate analysis offers a unique opportunity for characterizing the spatial and temporal dynamics of brain activity. However, whether measurements derived from this approach (e.g., temporal properties, transition probabilities, neural sources) show strong psychometric properties (i.e., reliability) during infancy is unknown and key information for advancing our understanding of how microstates are shaped by early life experiences and whether they relate to individual differences in infant abilities. A lack of methodological resources for performing microstate analysis of infant EEG has further hindered adoption of this cutting-edge approach by infant researchers. As a result, in the current study, we systematically addressed these knowledge gaps and report that most microstate-based measurements of brain organization and functioning except for transition probabilities were stable with four minutes of video-watching resting-state data and highly internally consistent with just one minute. In addition to these results, we provide a step-by-step tutorial, accompanying website, and open-access data for performing microstate analysis using a free, user-friendly software called Cartool. Taken together, the current study supports the reliability and feasibility of using EEG microstate analysis to study infant brain development and increases the accessibility of this approach for the field of developmental neuroscience.

Neurodevelopmental profile of infants and toddlers awaiting a kidney transplant.

Infants and toddlers with kidney failure are susceptible to neurodevelopmental delays due to medical comorbidities and rapid brain development in early childhood. However, research on the neuropsychological development of this patient population has been limited over the past 10years. We performed a retrospective study to evaluate the neurodevelopmental functioning of infants/toddlers with kidney failure who completed the Bayley Scales of Infant and Toddler Development (3rd and 4th Edition) as part of a pretransplant evaluation between 2010 and 2022 (n = 23; Mage = 18months, SD = 8.53; 16 males) using t-tests, linear model, and Pearson correlations. Mean Bayley scores of participants were below normative means for cognition (M = 86.74, 95% CI = 80.53-92.94, p < 0.001), language (M = 79.20, 95% CI = 73.32-85.08, p < 0.001), and motor (M = 78.00, 95% CI = 70.15-85.85, p < 0.001) domains. After adjusting for prematurity and epilepsy, patients on dialysis had significantly lower cognitive (78.7 vs. 93.8; p = 0.001) and motor scores (67.1 vs. 85.5; p = 0.01) compared to no dialysis. Pretransplant cognitive scores were positively correlated with posttransplant Full-Scale IQ (r(8) = 0.65 p = 0.04), verbal comprehension (r(8) = 0.75 p = 0.02), and fluid reasoning (r(7) = 0.68 p = 0.045). Similarly, pretransplant language scores were positively correlated with posttransplant Full-Scale IQ (r(7) = 0.74 p = 0.03) and verbal comprehension (r(7) = 0.73 p = 0.03). Of the 16 participants who reached age > 5years during the study period, seven were diagnosed with a neurodevelopmental disorder, including three with autism spectrum disorder. Infants and toddlers with kidney failure are at risk of developmental delays and later neurodevelopmental disorders. Dialysis is associated with cognitive and motor delays independent of prematurity and epilepsy.

First 1,000 Days Suncoast: Regional Initiative Transforming Care for Babies and Their Families

A child’s first 1,000 days are a period of rapid brain development; negative environments and stressful events can impact their lifelong health, well-being, resiliency, and prosperity. First 1,000 Days Suncoast is a tri-county initiative in southwest Florida comprising 90 partner organizations supporting families and babies by connecting them with resources and tools through a large and comprehensive network. Following the Collective Impact model, the region’s public community hospital was designated as the backbone organization, with a nurse-led team guiding the operations. A steering committee, with leaders of regional nonprofits and foundations, ensures tactical alignment with county priorities, and has been key in building a strong partner infrastructure. Three key components guide the activities of the initiative: care coordination; parent empowerment; and targeted interventions. Through collaboration with community professionals and parents, the initiative identifies the most pervasive barriers to care for families and develops innovative solutions. This method has led to system-wide transformations, organization-specific enhancements, and process improvements.

Neuron-derived exosomes mediate sevoflurane-induced neurotoxicity in neonatal mice via transferring lncRNA Gas5 and promoting M1 polarization of microglia.

Sevoflurane exposure during rapid brain development induces neuronal apoptosis and causes memory and cognitive deficits in neonatal mice. Exosomes that transfer genetic materials including long non-coding RNAs (lncRNAs) between cells play a critical role in intercellular communication. However, the lncRNAs found in exosomes derived from neurons treated with sevoflurane and their potential role in promoting neurotoxicity remain unknown. In this study, we investigated the role of cross-talk of newborn mouse neurons with microglial cells in sevoflurane-induced neurotoxicity. Mouse hippocampal neuronal HT22 cells were exposed to sevoflurane, and then co-cultured with BV2 microglial cells. We showed that sevoflurane treatment markedly increased the expression of the lncRNA growth arrest-specific 5 (Gas5) in neuron-derived extracellular vesicles, which inhibited neuronal proliferation and induced neuronal apoptosis by promoting M1 polarization of microglia and the release of inflammatory cytokines. We further revealed that the exosomal lncRNA Gas5 significantly upregulated Foxo3 as a competitive endogenous RNA of miR-212-3p in BV2 cells, and activated the NF-κB pathway to promote M1 microglial polarization and the secretion of inflammatory cytokines, thereby exacerbating neuronal damage. In neonatal mice, intracranial injection of the exosomes derived from sevoflurane-treated neurons into the bilateral hippocampi significantly increased the proportion of M1 microglia, inhibited neuronal proliferation and promoted apoptosis, ultimately leading to neurotoxicity. Similar results were observed in vitro in BV2 cells treated with the CM from HT22 cells after sevoflurane exposure. We conclude that sevoflurane induces the transfer of lncRNA Gas5-containing exosomes from neurons, which in turn regulates the M1 polarization of microglia and contributes to neurotoxicity. Thus, modulating the expression of lncRNA Gas5 or the secretion of exosomes could be a strategy for addressing sevoflurane-induced neurotoxicity.

THE ROLE OF EARLY CHILDHOOD EDUCATION IN PROMOTING LONG-TERM ACADEMIC SUCCESS

This article provides a comprehensive review of the role of early childhood education(ECE) in promoting long-term academic success. Early childhood is a critical period of rapid brain development and learning, making high-quality educational experiences during this time crucial for future academic achievement.The article explores the theoretical foundations of ECE, examines the key componenets of effective early childhood programs, and synthesizes empirical research on the long-term impacts of ECE on academic outcomes.Moreover, this paper aims to demonstrate the role of ECE in promoting long-term academic success by examining the social, emotional, and cognitive development of children.

A dataset of Chinese reading and brain development for children and adolescents

As a fundamental skill for children and adolescents, reading plays a crucial role in knowledge acquisition and cognitive development. Improving reading skills among children and adolescents is also the cornerstone of China’s national reading strategy. The rapid development of reading ability of children and adolescents coincides with their rapid brain development. Throughout the process of gradually acquiring reading skills, children and adolescents undergo various changes in neural activity and behavioral performance. However, the relationship between reading development and brain neurodevelopment of the brain still remains largely unknown. This paper offers valuable resources, including resting-state functional magnetic resonance imaging data, structural magnetic resonance imaging data, and comprehensive neuropsychological data from assessments of reading and cognitive-related tests in school-aged children and adolescents. It also includes preprocessed magnetic resonance imaging data, quality control report and description file. These valuable resources can significantly contribute to further scientific research in the field of neurodevelopment of reading in young individuals.

Ex-utero third trimester developmental changes in functional brain network organization in infants born very and extremely preterm.

The latter half of gestation is a period of rapid brain development, including the formation of fundamental functional brain network architecture. Unlike in-utero fetuses, infants born very and extremely preterm undergo these critical maturational changes in the extrauterine environment, with growing evidence suggesting this may result in altered brain networks. To date, however, the development of functional brain architecture has been unexplored. From a prospective cohort of preterm infants, graph parameters were calculated for fMRI scans acquired prior to reaching term equivalent age. Eight graph properties were calculated, Clustering Coefficient (C), Characteristic Path Length (L), Modularity (Q), Local Efficiency (LE), Global Efficiency (GE), Normalized Clustering (λ), Normalized Path Length (γ), and Small-Worldness (σ). Properties were first compared to values generated from random and lattice networks and cost efficiency was evaluated. Subsequently, linear mixed effect models were used to assess relationship with postmenstrual age and infant sex. A total of 111 fMRI scans were acquired from 85 preterm infants born at a mean GA 28.93 ± 2.8. Infants displayed robust small world properties as well as both locally and globally efficient networks. Regression models found that GE increased while L, Q, λ, γ, and σ decreased with increasing postmenstrual age following multiple comparison correction (r2Adj range 0.143-0.401, p < 0048), with C and LE exhibited trending increases with age. This is the first direct investigation on the extra-uterine formation of functional brain architecture in preterm infants. Importantly, our results suggest that changes in functional architecture with increasing age exhibit a different trajectory relative to in utero fetus. Instead, they exhibit developmental changes more similar to the early postnatal period in term born infants.

The Relationship between Depression Severity and Prefrontal Hemodynamic Changes in Adolescents with Major Depression Disorder: A Functional Near-infrared Spectroscopy Study.

: Numerous studies have identified hemodynamic changes in adults with major depressive disorder (MDD) by using functional near-infrared spectroscopy (fNIRS). However, studies on adolescents with MDD are limited. As adolescence is a stage of rapid brain development, differences may occur depending on age. This study used fNIRS as an objective tool to investigate hemodynamic changes in the frontal lobe according to depression severity and age in adolescents with MDD. : Thirty adolescents (12 aged 12-15 years and 18 aged 16-18 years) were retrospectively investigated. The Children's Depression Inventory was used as a psychiatric evaluation scale, fNIRS was used as an objective brain function evaluation tool, and the Verbal Fluency Test was performed. : During the Verbal Fluency Test, in the younger MDD group, oxygenated-hemoglobin concentration increased in the right dorsolateral prefrontal cortex region as the severity of depression increased. In the older MDD group, the oxygenated-hemoglobin concentration decreased in the right dorsolateral prefrontal cortex region as the severity of depression increased. : These results suggest that fNIRS may be an objective tool for identifying age differences among adolescents with MDD. To generalize the results and verify fNIRS as a potential biomarker tool, follow-up studies with a larger sample group should be conducted.

Implementation of Kindergarten Curriculum and the Pupil’s Acquisition of Basic Competencies

The term kindergarten came from a German origin that means “children’s garden. It serves as a transition period from home or preschool to formal education. The main purpose of kindergarten is to provide foundation for the child’s wholistic development. In Kindergarten program, children are engaged in different activities that are age appropriate. These activities are designed to promote the physical, cognitive, emotional and social development of children . Many research have shown that during the early years, rapid brain development occurred forming the foundation for future academic success. This stage is crucial because it is during this time that they develop the essential skills to prepare them for Grade 1 . This study sought to find out how the implementation of a kindergarten curriculum affects the readiness of our young learners for formal education. Several variables related to curriculum were considered in this study. These were the objectives of kindergarten curriculum in the Philippines, the Budget of Work provided by DepEd, the instructional materials used, the teacher’s competencies, learning environment and lesson planning. It was then correlated with the basic competencies expected from kinder pupils in terms of health and well-being, socioemotional development, language, literacy and communication (listening/viewing, speaking, reading, writing), mathematics and understanding the physical and natural environment. This research was conducted in the Schools Division of San Pablo wherein 70 kindergarten teachers from public schools were the respondents. The research method used wasa quantitative descriptive method with Pearson product-moment correlation. The result showed that there was a significant relationship between the implementation of the curriculum and the pupils acquired basic competencies.

What Is Rejection? Lexical, Experimental, and Analytical Specificity Is Needed to Drive Developmental Psychopathology Research Forward

There is increasing urgency in the quest to identify prospective risk factors for nonsuicidal self-injury (NSSI), driven by a growing teen mental health crisis. NSSI, which involves deliberately harming one’s physical body without suicidal intent, increases rapidly in early to middle adolescence and is a risk factor for suicidality and other mental illness ( 1 Nock M.K. Joiner Jr., T.E. Gordon K.H. Lloyd-Richardson E. Prinstein M.J. Non-suicidal self-injury among adolescents: Diagnostic correlates and relation to suicide attempts. Psychiatry Res. 2006; 144: 65-72 Crossref PubMed Scopus (1014) Google Scholar ). Accumulating research highlights social (e.g., rejection, poor relationships, low support) and affective (e.g., reactivity, lability, dysregulation) risk mechanisms, among others ( 2 Cipriano A. Cella S. Cotrufo P. Nonsuicidal self-injury: A systematic review. Front Psychol. 2017; 8: 1946 Crossref PubMed Scopus (224) Google Scholar ). However, social and affective risk mechanisms can be linked and may interact to confer risk for NSSI as well as mental illness more broadly ( 3 Hsu D.T. Jarcho J.M. Next up for psychiatry: Rejection sensitivity and the social brain. Neuropsychopharmacology. 2021; 46: 239-240 Crossref Scopus (8) Google Scholar ). This is particularly relevant in adolescence, a time of rapid brain development and increases in both mental health struggles and reliance on peer affiliation ( 4 Guyer A.E. Adolescent psychopathology: The role of brain-based diatheses, sensitivities, and susceptibilities. Child Dev Perspect. 2020; 14: 104-109 Crossref PubMed Scopus (19) Google Scholar ). Despite the recognition that social difficulties are a common correlate of mental illness, few studies integrate robust measures of real-world peer experience within a neuroscience framework to prospectively predict the emergence of adolescent mental health struggles. Understanding whether neural diatheses confer increased vulnerability to specific stressful peer experiences in adolescence is a critical open question—interventions designed to target neural diatheses or to promote specific types of peer experiences may be critical for prevention efforts in the future ( 4 Guyer A.E. Adolescent psychopathology: The role of brain-based diatheses, sensitivities, and susceptibilities. Child Dev Perspect. 2020; 14: 104-109 Crossref PubMed Scopus (19) Google Scholar ). SEE CORRESPONDING ARTICLE ON PAGE 40 SEE CORRESPONDING ARTICLE ON PAGE 40 Neural Reactivity to Social Punishment Predicts Future Engagement in Nonsuicidal Self-injury Among Peer-Rejected AdolescentsBiological PsychiatryVol. 94Issue 1PreviewRates of nonsuicidal self-injury (NSSI) increase dramatically in adolescence. Affective reactivity and adverse social experiences have been linked to NSSI, but less is known about whether these factors may separately or interactively predict NSSI, especially longitudinally. This study combined functional magnetic resonance imaging and a sociometric measure to test whether a combination of neural (e.g., amygdala) reactivity to social punishment and peer-nominated peer acceptance/rejection predicts NSSI longitudinally in adolescence. Full-Text PDF

Screen time and speech and language delay in children aged 12–48 months in UAE: a case–control study

BackgroundTo identify impact of screen time on speech and language development in preschool children. There has been an alarming increase in the use of electronic devices among preschool children despite their potential adverse effects on childhood development during this crucial time of rapid brain development. Prior research has identified the potential risk and benefits of traditional screen media such as television and video. Our findings will help your readers understand the potential impact of screen time between traditional and new technologies. The case–control study included 227 new patients with language delay and 227 normal children, aged 12–48 months male and female. Language delay was diagnosed by reviewing language milestones and Receptive-Expressive Emergent Language Test (RELT). Television viewing variables and child/parental characteristics between both groups were interviewed. Odds ratio was used to establish whether screen time using either electronic devices (smartphones and tablets) or TV viewing has an effect on speech and language development. Chi-square test was used to establish the association between categorical variable 95%. A P-value less than 0.05 was considered to be statistically significant.ResultA total of 90.3% of those who have speech and language developmental delay use electronic devices. Odd ratio is found to be statistically significant.ConclusionThe factors that predict language delays include use of and early onset of using an electronic device at 12–24 months of age. The factors that were less likely associated with language delays are watching TV and the mother’s education level.

Sleep across the first year of life is prospectively associated with brain volume in 12-months old infants

ObjectiveLonger sleep duration in infancy supports cognitive and affective functioning – likely through effects on brain development. From childhood through old age, there is evidence for a close link between sleep and brain volume. However, little is known about the association between sleep duration and brain volume in infancy, a developmental period of unprecedented brain maturation. This study aimed to close this gap by assessing sleep duration across the first year of life and gray and white matter volume at 12-mo age. MethodInfant sleep duration trajectories across the first year of life were based on maternal reports at 1, 3, 6, 9, and 12 months of age. Infant specific trajectories were generated by running a logarithmic regression for each infant and residualizing the resulting slopes for their intercept. Structural magnetic resonance imaging (MRI) scans were acquired at 12-mo age. Gray and white matter volume estimates were residualized for intracranial volume and age at scan. ResultsData to calculate sleep trajectories was available for 112 infants. Overall, sleep duration decreased over the course of the first year of life and was best described by a logarithmic function. Of these infants, data on brain volume was available for 45 infants at 12-mo age. Infants whose sleep duration decreased less during the first year of life relative to their intercept had, on average, greater white matter volume (β = .36, p = .02). Furthermore, average sleep duration across the first year of life, and sleep duration specifically at 6 and 9 months were positively associated with white matter volume. Sleep duration during the first year of life was not significantly associated with gray matter volume at 12-mo age. ConclusionSufficient sleep duration may benefit infant white matter development – possibly by supporting myelination. The fact that sleep duration was not associated with gray matter volume is in line with preclinical studies suggesting that sleep may be crucial for the balance between synaptogenesis and synaptic pruning but not necessarily relate to a net increase in gray matter volume. Supporting sleep during periods of rapid brain development and intervening in case of sleep problems may have long-term benefits for cognitive function and mental health.

Neurotransmitter disturbances caused by methylmercury exposure: Microbiota-gut-brain interaction

The fetal and early postnatal stages are periods of rapid brain development, during which, methylmercury (MeHg) exposure can cause lasting cognitive impairments. MeHg exposure disrupts neurotransmitter metabolites, which increased susceptibility to neurological responses. However, the neurotoxic mechanism underlying the MeHg-induced disruption of neurotransmitter metabolism requires further exploration. To this end, female Sprague-Dawley (SD) rats were administered NaCl (control group) or MeHg (0.6 mg/kg, 1.2 mg/kg and 2.4 mg/ kg body weight (bw), where the body weight refers to the dams) during the perinatal period, and then changes in neurotransmitter profiles and the gut microbiota of offspring were detected. The results showed that tryptophan (Trp) and tyrosine (Tyr) pathway neurotransmitter metabolites, including serotonin (5-HT), 5-hydroxy indole acetic acid (5-HIAA), N-acetyl-5-hydroxytryptamin (NAS), Tyr, dopamine (DA) and epinephrine (E), were significantly changed, and the Kynurenine/Tryptophan (Kyn/Trp) ratio was increased in the MeHg-treated groups. Meanwhile, acetylcholine (ACh) and neurotransmitters involved in the amino acid pathway were significantly reduced. Notably, MeHg treatment induced a significant reduction in tight junctions in the colon and hippocampal tissue. Furthermore, fecal microbiota analysis indicated that the diversity and composition characteristics were significantly altered by MeHg exposure. Mediation analysis showed that the gut microbiota mediated the effect of MeHg treatment on the neurotransmitter expression profiles. The present findings shed light on the regulatory role of the gut microbiota in MeHg-disrupted neurotransmitter metabolic pathways and the potential impact of perinatal MeHg treatment on the “cross-talk” between the gut and brain.

Long-Chain Polyunsaturated Fatty Acid Levels in Formulae Influence Deposition of Docosahexaenoic Acid and Arachidonic Acid in Brain and Red Blood Cells of Artificially Reared Neonatal Rats

We studied the effects of dietary long-chain polyunsaturated fatty acids (PUFA) on the fatty acid composition of the brain and red blood cells in gastrostomized rat pups reared artificially from postnatal Days 5–18. These pups were fed rat milk substitutes in which the fat comprised 10% linoleic acid and 1% α-linolenic acid and, using a 3 × 3 factorial design, one of three levels of both arachidonic acid (AA) and docosahexaenoic acid (DHA) supplied as single cell microbial oils (0.0, 0.4 and 2.4% fatty acids). A tenth group was reared by nursing dams. The fatty acid composition of the phosphatidylethanolamine (PE) and phosphatidylserine/phosphatidylinositol (PS/PI) phospholipids in the brain and red blood cells on Day 18 reflected the dietary composition in that pups receiving long-chain supplementation of each had higher levels of the supplemented PUFA, but lower levels of the other, relative to unsupplemented groups. In contrast to these results, there were few changes in the brain in phosphatidylcholine (PC) phospholipids whereas, in the red blood cells, changes in PC were similar to those in PE and PS/PI. Regression analyses showed that DHA levels in the brain correlated more closely with those of the red blood cells than did AA levels. The results of this study indicate that, although supplementation of formula with AA or DHA during the period of rapid brain development in rats increases deposition of the long-chain PUFA in the developing tissues, each also affects the levels of the other.

The effects of puberty and sex on adolescent white matter development: A systematic review

Adolescence, the transition between childhood and adulthood, is characterized by rapid brain development in white matter (WM) that is attributed in part to rising levels in adrenal and gonadal hormones. The extent to which pubertal hormones and related neuroendocrine processes explain sex differences in WM during this period is unclear. In this systematic review, we sought to examine whether there are consistent associations between hormonal changes and morphological and microstructural properties of WM across species and whether these effects are sex-specific. We identified 90 (75 human, 15 non-human) studies that met inclusion criteria for our analyses. While studies in human adolescents show notable heterogeneity, results broadly demonstrate that increases in gonadal hormones across pubertal development are associated with macro- and microstructural changes in WM tracts that are consistent with the sex differences found in non-human animals, particularly in the corpus callosum. We discuss limitations of the current state of the science and recommend important future directions for investigators in the field to consider in order to advance our understanding of the neuroscience of puberty and to promote forward and backward translation across model organisms.