Neurodevelopmental Processes Research Articles

Cannabis use in youth is associated with chronic inflammation.

Markers of inflammation and cannabis exposure are associated with an increased risk of mental disorders. In the current study, we investigated associations between cannabis use and biomarkers of inflammation. Utilizing a sample of 914 participants from the Avon Longitudinal Study of Parents and Children, we investigated whether interleukin-6 (IL-6), tumor necrosis factor α (TNFα), C-reactive protein (CRP), and soluble urokinase plasminogen activator receptor (suPAR) measured at age 24 were associated with past year daily cannabis use, less frequent cannabis use, and no past year cannabis use. We adjusted for a number of covariates including sociodemographic measures, body mass index, childhood trauma, and tobacco smoking. We found evidence of a strong association between daily or near daily cannabis use and suPAR. We did not find any associations between less frequent cannabis use and suPAR. We did not find evidence of an association between IL-6, TNFα or CRP, and cannabis use. Our finding that frequent cannabis use is strongly associated with suPAR, a biomarker of systemic chronic inflammation implicated in neurodevelopmental and neurodegenerative processes is novel. These findings may provide valuable insights into biological mechanisms by which cannabis affects the brain and impacts the risk of serious mental disorders.

Dopamine-mediated behavioral alterations following exposure to a social video in socially isolated mice during the developmental period.

Video exposure is known to affect brain function, yet its impact on neurodevelopmental processes remains unclear. This study aimed to investigate whether exposure to a video depicting social behavior induces behavioral and neurological changes in socially isolated mice. On Postnatal Day (PND) 21, male mice were separated from their dams and randomly assigned to three groups: socially grouped mice; socially isolated mice (ISO), where mice were housed without any social stimulation; and social video-exposed mice (SVE), where mice were exposed to a social video played on a tablet from PND21 to PND56 under socially isolated conditions. On PND56, all animals underwent behavioral tests. Compared to the socially grouped mice and ISO group, the SVE group showed an attenuated response to amphetamine treatment. In the social cognition test, the ISO group exhibited decreased affiliative behavior and increased offensive and defensive behavior. However, the SVE group showed a partial improvement in social cognition, including increased affiliative behaviors and decreased defensive behaviors, although no changes in offensive behaviors were observed. Furthermore, the SVE group exhibited elevated levels of tyrosine hydroxylase and dopamine transporter in key social cognition regions-namely the prefrontal cortex, retrosplenial cortex, and hippocampus. This neurochemical shift implies that socially isolated mice can acquire social behaviors through exposure to video-based social interactions. These effects may be related to the compensatory response of the dopamine system, which is implicated in various psychiatric disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A bibliometric analysis of studies on environmental enrichment spanning 1967-2024: patterns and trends over the years.

Environmental Enrichment (EE) has received considerable attention for its potential to enhance cognitive and neurobiological outcomes in animal models. This bibliometric analysis offers a comprehensive evaluation of the EE research spanning from 1967 to 2024, utilizing data extracted from Scopus and analyzed through R and VOSviewer. The volume of publications, citation patterns, and collaborations were systematically reviewed, highlighting important contributions and emerging trends within the field of animal research. Core concepts of EE research are mapped, revealing key themes such as neuroplasticity, cognitive function, and behavioral outcomes. A significant increase in EE research is demonstrated, particularly after the year 2000, reflecting growing scientific and public interest in EE paradigms. This analysis provides insights into the global contributions and collaborative networks that have shaped EE studies over time. The role of EE in advancing the understanding of neurobiological, neurodevelopmental, and neurodegenerative processes is underscored. Influential contributors, leading countries, and high-impact journals in the field of EE are identified, offering a valuable resource for researchers seeking to understand or extend the current knowledge base. The strategic selection of keywords and rigorous data curation methods ensure that the findings accurately reflect the most impactful aspects of EE research in animals. This study serves as an essential reference for future explorations and applications of EE across disciplines. By providing a clear and structured overview of the field, this paper aims to serve as a foundation for ongoing and future research initiatives, encouraging more robust investigations and applications of EE to enhance cognitive and neurological health globally.

Rapid effects of valproic acid on the fetal brain transcriptome: implications for brain development and autism

There is an increased incidence of autism among the children of women who take the anti-epileptic, mood-stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration to the pregnant dam revealed that VPA rapidly and significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed. Expression of 399 autism risk genes was significantly altered by VPA as was expression of 258 genes that have been reported to modulate fetal brain development but are not otherwise linked to autism. Expression of genes associated with intracellular signaling pathways, neurogenesis, and excitation-inhibition balance as well as synaptogenesis, neuronal fate determination, axon and dendritic development, neuroinflammation, circadian rhythms, and epigenetic modulation of gene expression was dysregulated by VPA. Notably, at least 40 genes that are known to regulate embryonic neurogenesis were dysregulated by VPA. The goal of this study was to identify mouse genes that are: (a) significantly up- or downregulated by VPA in the fetal brain and (b) associated with autism and/or known to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity and, consequently behavior, in the adult. The genes meeting these criteria provide potential targets for future hypothesis-driven studies to elucidate the proximal causes of errors in brain connectivity underlying neurodevelopmental disorders such as autism.

Sex-specific DNA methylation signatures of autism spectrum disorder in newborn blood.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental conditions currently diagnosed by behavioral assessment in childhood, although neuropathology begins during gestation. A poorly understood male bias for ASD diagnosis is thought to be due to both biological sex differences and cultural biases against female diagnosis of ASD. Identification of molecular biomarkers of ASD likelihood in newborns would provide more objective screening and early intervention. Epigenetic dysregulation has been reported in multiple tissues from newborns who are later diagnosed with ASD, but this is the first study to investigate sex-specific DNA methylation signatures for ASD in newborn blood, an accessible and widely banked tissue. DNA methylation was assayed from ASD and typically developing (TD) newborn blood (discovery set n = 196, replication set n = 90) using whole genome bisulfite sequencing (WGBS) . Sex-stratified differentially methylated regions (DMRs) were assessed for replication, comparisons by sex, overlaps with DMRs from other tissues, and enrichment for biological processes and SFARI ASD-risk genes. We found that newborn blood ASD DMRs from both sexes significantly replicated in an independent cohort and were enriched for hypomethylation in ASD compared to TD samples, as well as location in promoters, CpG islands and CpG shores. Comparing females and males, we found that most DMRs with sex differences amongst TD individuals were also found in ASD individuals, plus many additional DMRs with sex differences that were only found in those with ASD. Newborn blood DMRs from females were enriched for the X chromosome and both sexes showed significant overlap with DMRs from umbilical cord blood and placenta but not post-mortem cortex. DMRs from all tissues were enriched for neurodevelopmental processes (females) and SFARI ASD-risk genes (females and males). This study is primarily limited by sample sizes, particularly amongst females. Overall, we found a highly replicated sex-specific DNA methylation signature of ASD in newborn blood that showed support for the female protective effect and convergence with epigenetic and genetic signatures of ASD in newborns. These results demonstrate the utility of newborn blood in ASD screening and emphasizes the importance of sex-stratification in future studies.

Prenatal social disadvantage is associated with alterations in functional networks at birth

Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth. As part of the Early Life Adversity and Biological Embedding study, mothers were recruited during pregnancy, prenatal social disadvantage was assessed across trimesters, and their healthy, full-term offspring were imaged using resting-state functional magnetic resonance imaging during the first weeks of life. Multivariate machine learning methods revealed that neonatal functional connectivity (FC) varied as a function of prenatal exposure to social disadvantage (n = 261, R = 0.43, R2 = 0.18), with validation in an independent sample. Alterations in FC associated with prenatal social disadvantage occurred brain-wide and were most pronounced in association networks (fronto-parietal, ventral attention, dorsal attention) and the somatomotor network. Amygdala FC was altered at birth, with a pattern shared across subcortical structures. These findings provide critical insights into how early in development functional networks begin to diverge in the context of social disadvantage and elucidate the functional networks that are most impacted.

The Development of Socially Directed Attention: A Functional Magnetic Resonance Imaging Study in Infant Monkeys.

Socially guided visual attention, such as gaze following and joint attention, represents the building block of higher-level social cognition in primates, although their neurodevelopmental processes are still poorly understood. Atypical development of these social skills has served as early marker of autism spectrum disorder and Williams syndrome. In this study, we trace the developmental trajectories of four neural networks underlying visual and attentional social engagement in the translational rhesus monkey model. Resting-state fMRI (rs-fMRI) data and gaze following skills were collected in infant rhesus macaques from birth through 6 months of age. Developmental trajectories from subjects with both resting-state fMRI and eye-tracking data were used to explore brain-behavior relationships. Our findings indicate robust increases in functional connectivity (FC) between primary visual areas (primary visual cortex [V1] - extrastriate area 3 [V3] and V3 - middle temporal area [MT], MT and anterior superior temporal sulcus area [AST], as well as between anterior temporal area [TE]) and amygdala (AMY) as infants mature. Significant FC decreases were found in more rostral areas of the pathways, such as between temporal area occipital part - TE in the ventral object pathway, V3 - lateral intraparietal (LIP) of the dorsal visual attention pathway and V3 - temporo-parietal area of the ventral attention pathway. No changes in FC were found between cortical areas LIP-FEF and temporo-parietal area - Area 12 of the dorsal and ventral attention pathways or between Anterior Superior Temporal sulcus area (AST)-AMY and AMY-insula. Developmental trajectory of gaze following revealed a period of dynamic changes with gradual increases from 1 to 2 months, followed by slight decreases from 3 to 6 months. Exploratory association findings across the 6-month period showed that infants with higher gaze following had lower FC between primary visual areas V1-V3, but higher FC in the dorsal attention areas V3-LIP, both in the right hemisphere. Together, the first 6 months of life in rhesus macaques represent a critical period for the emergence of gaze following skills associated with maturational changes in FC of socially guided attention pathways.

Unraveling the heart-brain axis: shared genetic mechanisms in cardiovascular diseases and Schizophrenia

The comorbidity between cardiovascular diseases (CVD) and schizophrenia (SCZ) has attracted widespread attention from researchers, with shared genetic causes potentially providing important insights into their association. This study conducted a comprehensive analysis of genetic data from 17 types of CVD and SCZ using genome-wide multi-trait association studies (GWAS), employing statistical methods such as LDSC, MTAG, LAVA, and bidirectional Mendelian randomization to explore global and local genetic correlations and identify pleiotropic single nucleotide variants (SNVs). The analysis revealed a significant genetic correlation between CVD and SCZ, identifying 842 potential pleiotropic single nucleotide variants (SNVs) and multiple associated biological pathways. Notably, genes such as TRIM27, CENPM, and MYH7B played critical roles in the shared genetic variations of both types of diseases. This study reveals the complex genetic relationship between CVD and SCZ, highlighting potential shared biological mechanisms involving immune responses, metabolic factors, and neurodevelopmental processes, thereby providing new directions for future interventions and treatments.

Functional gradient dysfunction in drug-naïve first-episode schizophrenia and its correlation with specific transcriptional patterns and treatment predictions

Abstract Background First-episode schizophrenia (FES) is a progressive psychiatric disorder influenced by genetics, environmental factors, and brain function. The functional gradient deficits of drug-naïve FES and its relationship to gene expression profiles and treatment outcomes are unknown. Methods In this study, we engaged a cohort of 116 FES and 100 healthy controls (HC), aged 7 to 30 years, including 15 FES over an 8-week antipsychotic medication regimen. Our examination focused on primary-to-transmodal alterations in voxel-based connection gradients in FES. Then, we employed network topology, Neurosynth, postmortem gene expression, and support vector regression to evaluate integration and segregation functions, meta-analytic cognitive terms, transcriptional patterns, and treatment predictions. Results FES displayed diminished global connectome gradients (Cohen's d = 0.32–0.57) correlated with compensatory integration and segregation functions (Cohen's d = 0.31–0.36). Predominant alterations were observed in the default (67.6%) and sensorimotor (21.9%) network, related to high-order cognitive functions. Furthermore, we identified notable overlaps between partial least squares (PLS1) weighted genes and dysregulated genes in other psychiatric conditions. Genes linked with gradient alterations were enriched in synaptic signaling, neurodevelopment process, specific astrocytes, cortical layers (layer II and IV), and developmental phases from late/mid fetal to young adulthood. Additionally, the onset age influenced the severity of FES, with discernible differences in connection gradients between minor- and adult-FES. Moreover, the connectivity gradients of FES at baseline significantly predicted treatment outcomes. Conclusions These results offer significant theoretical foundations for elucidating the intricate interplay between macroscopic functional connection gradient changes and microscopic transcriptional patterns during the onset and progression of FES.

Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis

Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity. Therefore, using data collected during the 8-center North American Prodrome Longitudinal Study (NAPLS-2), we explored relationships between MMN amplitudes and salivary cortisol, gray matter volumes, and inflammatory cytokines. Participants included 303 CHR-P individuals with baseline electroencephalography (EEG) data recorded during an MMN paradigm as well as structural magnetic resonance imaging (MRI) and salivary cortisol, of which a subsample (n = 57) also completed blood draws. More deficient MMN amplitudes were associated with greater salivary cortisol and pro-inflammatory cytokine levels in future CHR-Converters, but not among those who did not convert to psychosis within the next two years. More deficient MMN amplitude was also associated with smaller total gray matter volume across participants regardless of future clinical outcomes, and with subcortical gray matter volumes among future CHR-Converters only. These findings are consistent with the theory that deficient NMDAR-dependent plasticity results in an overabundance of weak synapses that are subject to over-pruning during psychosis onset, contributing to gray matter loss. Further, MMN plasticity mechanisms may interact with stress, cortisol, and neuroinflammatory processes, representing a proximal influence of psychosis.

Environmental risks and etiology for schizophreniafromthelens of neurodevelopment: A literature review

Abstract. Schizophrenia is a chronic mental disorder marked by positive symptoms such as hallucinations and delusions, negative symptoms including aversion and withdrawal, and cognitive dysfunctions. Despite the preponderance of genetic influences, environmental factors have rarely been singled out in the past literature as significantly contributing to the development of the disorder. This paper focuses on major environmental risk factors, such as prenatal infections and malnutrition, urban living, childhood trauma, and substance abuse, which examines the impact from a neurodevelopmental perspective. Findings from epidemiologic and neuroimaging studies indicate that these environmental factors disrupt crucial neurodevelopmental processes and potentially increase the risk of developing schizophrenia. Neuroimaging advances have provided insights into brain abnormalities associated with schizophrenia that could facilitate early diagnosis and intervention. However, further longitudinal and interdisciplinary studies are currently required to adequately understand the role of environmental factors in the etiology of schizophrenia.

Air pollution: an emerging risk factor for autism spectrum disorder

The global surge in air pollution poses an increasingly concerning environmental risk factor for neurodevelopmental disorders, particularly autism spectrum disorder (ASD). Recent epidemiological studies have revealed compelling associations between exposure to specific air pollutants, including fine particulate matter (PM), nitrogen oxides (NO, NO2), sulfur dioxide (SO2) and ozone (O3), and increased ASD risk. While the rising global ASD prevalence, now affecting 1%–1.5% of the population, partially reflects expanded diagnostic criteria and enhanced screening, mounting evidence points to the critical role of gene–environment interactions in ASD etiology. Air pollutants can trigger multiple pathogenic mechanisms, including neuroinflammation, oxidative/nitrosative stress, epigenetic modifications, and glutamatergic/GABAergic neurotransmitter system disruption. The timing of exposure appears crucial, with heightened vulnerability during prenatal development and early childhood when critical neurodevelopmental processes, such as neuronal migration, synaptogenesis, and myelination occur. Research priorities should focus on how air pollutants affect brain development in genetically susceptible individuals, especially during pregnancy and early childhood. Better ways are needed to identify individuals at the highest risk and develop practical protective measures. Given the rising global pollution levels, this knowledge will help shape meaningful public health policies to protect future generations from environmental factors that may contribute to ASD.

CNSC-10. WHEN GOOD THINGS GO OFF TRK: THE INTERSECTION OF NEUROSCIENCE & ONCOLOGY

Abstract How and why do processes and molecular players that were once an integral part of normal neurodevelopment go awry in pathological conditions, such as cancer? Embryogenesis, and neurodevelopment in particular, comprise an elegant and well-orchestrated series of tightly regulated events, culminating in an organized and highly functioning organism. Cancer, on the other hand, can often be viewed as an uncontrolled, unrestrained, genetically chaotic disease, lacking the precise spatial and temporal rigidity associated with normal development. While appearing to be on opposite sides of the organizational spectrum, the similarities between early neurodevelopment and oncogenesis are numerous. The link between developmental signaling and cancer initiation, maintenance, and metastasis has long been known for several members of the Wnt, Hedgehog, and Notch pathways and years of gene-level analyses have provided a wealth of knowledge and mechanistic insight. As advances in next generation sequencing allow for deeper characterization of genetic programs, it is increasingly possible to explore various isoforms of cancer associated genes. It is widely known that neurotrophins and their receptors (TrkA, TrkB, TrkC) are instrumental for neurodevelopment and that they remain critical for proper neuronal functioning throughout life. Our work highlights a previously unidentified role for an alternatively spliced neurotrophin receptor in neurodevelopment, embryogenesis, transformation, and oncogenesis across multiple tumor types in humans and mice. This specific isoform, TrkB.T1, is the predominant NTRK2 isoform across embryonic organogenesis, and forced overexpression of this embryonic pattern causes multiple solid and nonsolid tumors in mice. TrkB.T1 also emerges as the predominant NTRK isoform expressed in a wide range of adult and pediatric tumors, including those harboring various NTRK fusions. This work hopes to address the fundamental question of how neurodevelopmental processes can go awry in cancer, while seeking to better characterize the role of TRKs, in normal developmental processes and oncogenesis.

Applying Cognitive Neuroscience to Juvenile Justice: The Role of Brain Development in Decision-Making

The intersection of cognitive neuroscience and juvenile justice offers profound insights into understanding the role of brain development in decision-making among adolescents. This research explores the implications of neurodevelopmental processes, particularly in the prefrontal cortex and limbic system, which govern impulse control, risk assessment, and emotional regulation. Adolescents are at a stage of heightened neuroplasticity, which significantly influences their cognitive and emotional responses. This study examines how these developmental factors impact their decision-making and susceptibility to external influences, such as peer pressure. By integrating neuroscientific findings with legal frameworks, the research highlights the importance of adopting rehabilitative over punitive approaches in juvenile justice systems. The findings underscore the need for tailored interventions and policies that account for the neurobiological underpinnings of adolescent behavior, fostering a balance between accountability and the opportunity for growth and rehabilitation.

Exploring Sex-Based Neuropsychological Outcomes in Pediatric Brain Cancer Survivors: A Pilot Study.

The increasing survival rates among pediatric cancer patients underscore the critical need to understand the long-term psychosocial impacts of cancer treatments, such as cisplatin and carboplatin. While these treatments are lifesaving, they may pose risks to neurodevelopmental processes. Despite the substantial body of research highlighting cognitive impairments associated with cancer treatments, there remains a gap in understanding how these effects differ by sex. As sex differences could inform tailored interventions and support mechanisms for affected individuals, this pilot study aimed to examine the sex differences in neuropsychological outcomes in patients treated for brain cancer with cisplatin and/or carboplatin. Our study employed rigorous/structured neuropsychological assessments to evaluate executive functions in pediatric cancer survivors treated with cisplatin and/or carboplatin. We utilized the BRIEF and TOL tests to assess the key domains of executive function, including inhibitory control, cognitive flexibility, and problem-solving abilities. Additionally, psychosocial factors were evaluated using the Resiliency Scale to measure resilience and the PAT test to assess family psychosocial risk. In our cohort of 17 patients, significant sex differences emerged, where males outperformed females in areas such as inhibitory control, impulse regulation, and strategic planning. These findings highlight the complexity of cognitive outcomes in pediatric cancer survivors. Understanding sex-specific differences is essential for developing tailored interventions that optimize cognitive and psychosocial outcomes. Future research should focus on larger cohorts and longitudinal studies to validate these findings and guide targeted interventions to improve survivorship outcomes.

ANGI-09. GRAPH NETWORK ANALYSIS IDENTIFIES GENETIC COMMUNITIES OF CSF2RA AND RBFOX1 AS REGULATORS OF INVASIVE HIGH-GRADE GLIOMA BIOLOGY

Abstract BACKGROUND High-grade glioma (HGG) is the most common and aggressive form of primary brain cancer. Standard of care surgery employs Magnetic Resonance Imaging to identify the contrast enhancing (CE) core for resection, leaving a non-enhancing (NE) invasive rim of tumor which contributes to recurrence. Recent multi-omics analyses identified predominant neuronal and immune signatures within NE tumor. Here, we apply a graph network to integrate regionally heterogeneous data from a unique dataset of spatially-localized CE and NE biopsies from a large cohort of patients with HGG. METHODS RNA-sequencing of 1159 differentially expressed genes across 159 IDH-wt biopsies (74 patients) from NE/CE regions were represented as nodes in a Neo4j network. Candidate genes for network random walks occurred exclusively within NE communities detected by modularity optimization and localized by cell-type using single-cell RNA-sequencing (scRNAseq). CSF2RA and RBFOX1 were selected as sources (walk length = 5; 10,000 walks/source node). Frequently occurring genes (one-tailed test) in walks were ranked by correlation with CSF2RA/RBFOX1 expression in NE samples and analyzed by gene set enrichment analysis for biological processes (clusterProfiler). Random walk genes were visualized (DoHeatmap) against composite NE/CE scRNAseq profiles. RESULTS CSF2RA and RBFOX1 were upregulated in NE samples (logFC = 0.789, 1.85). Upregulation of CSF2RA, an immune receptor, in the Glycolytic/Plurimetabolic and RBFOX1, a neurodevelopmental regulator, in the Neuronal glioma subtypes were observed in NE samples (ANOVA p < 0.05). CSF2RA walk genes (n=46) enriched metabolic/proliferative signatures, while RBFOX1 walk genes (n=201) showed neurodevelopmental upregulation. scRNAseq localized CSF2RA to monocytes/macrophages while RBFOX1 was expressed in distinct astrocyte/neuroepithelial populations. CONCLUSION CSF2RA and RBFOX1’s gene networks modulate immune and neurodevelopmental processes influencing glioma progression in NE tumor. Understanding the region-specific roles of these networks may offer strategies for targeting cells in the invasive glioma rim.

Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A.

Neurons are exceptionally sensitive to oxidative stress, which is the basis for many neurodegenerative disease pathophysiologies. The posttranscriptional basis for neuronal differentiation and behavior is not well characterized. The steady-state levels of mRNA are outcomes of an interplay between RNA transcription and decay. However, the correlation between mRNA transcription, translation, and stability remains elusive. We utilized a SH-SY5Y-based neural differentiation model that is widely used to study neurodegenerative diseases. After neuronal differentiation, we observed enhanced sensitivity of mature neurons to mitochondrial stresses and ferroptosis induction. We employed a newly developed simplified mRNA stability profiling technique to explore the role of mRNA stability in SH-SY5Y neuronal differentiation model. Transcriptome-wide mRNA stability analysis revealed neural-specific RNA stability kinetics. Our analysis revealed that mRNA stability could either exert the buffering effect on gene products or change in the same direction as transcription. Importantly, we observed that changes in mRNA stability corrected over or under transcription of mRNAs to maintain mRNA translation dynamics. Furthermore, we conducted integrative analysis of our mRNA stability data set, and a published CRISPR-i screen focused on neuronal oxidative stress responses. Our analysis unveiled novel neuronal stress response genes that were not evident at the transcriptional or translational levels. SEPHS2 emerged as an important neuronal stress regulator based on this integrative analysis. Motif analysis unveiled SAMD4A as a major regulator of the dynamic changes in mRNA stability observed during differentiation. Knockdown of SAMD4A impaired neuronal differentiation and influenced the response to oxidative stress. Mechanistically, SAMD4A was found to alter the stability of several mRNAs. The novel insights into the interplay between mRNA stability and cellular behaviors provide a foundation for understanding neurodevelopmental processes and neurodegenerative disorders and highlight dynamic mRNA stability as an important layer of gene expression.

Effects of parental socioeconomic status on offspring's fetal neurodevelopment.

Emerging evidence underscores the prenatal period's critical role in shaping later cognition and health, influenced by an intricate interplay of parental genetic and environmental factors. Birth weight is commonly used as a retrospective indicator of fetal development, but recent focus has shifted to more specific proxies of neurodevelopment, like cortical sulcal patterns, which are established in utero and remain stable after birth. This study aimed to elucidate the interrelated effects of parental socioeconomic status, brain volume, birth weight, and sulcal patterns in the anterior cingulate cortex. Utilizing structural Magnetic Resonance Imaging (MRI), parental educational attainment, and related polygenic risk scores, the study analyzed 203 healthy right-handed participants aged 9 to 18. Structural equation modeling demonstrated that the anterior cingulate cortex sulcal pattern is influenced by parental socioeconomic status and global brain volume, with socioeconomic status correlating with a polygenic risk score. These findings suggest that prenatal neurodevelopmental processes may mediate the intergenerational transmission of inequalities.

The microbiota: a key regulator of health, productivity, and reproductive success in mammals.

The microbiota, intensely intertwined with mammalian physiology, significantly impacts health, productivity, and reproductive functions. The normal microbiota interacts with the host through the following key mechanisms: acting as a protective barrier against pathogens, maintain mucosal barrier integrity, assisting in nutrient metabolism, and modulating of the immune response. Therefore, supporting growth and development of host, and providing protection against pathogens and toxic substances. The microbiota significantly influences brain development and behavior, as demonstrated by comprehensive findings from controlled laboratory experiments and human clinical studies. The prospects suggested that gut microbiome influence neurodevelopmental processes, modulate stress responses, and affect cognitive function through the gut-brain axis. Microbiota in the gastrointestinal tract of farm animals break down and ferment the ingested feed into nutrients, utilize to produce meat and milk. Among the beneficial by-products of gut microbiota, short-chain fatty acids (SCFAs) are particularly noteworthy for their substantial role in disease prevention and the promotion of various productive aspects in mammals. The microbiota plays a pivotal role in the reproductive hormonal systems of mammals, boosting reproductive performance in both sexes and fostering the maternal-infant connection, thereby becoming a crucial factor in sustaining mammalian existence. The microbiota is a critical factor influencing reproductive success and production traits in mammals. A well-balanced microbiome improves nutrient absorption and metabolic efficiency, leading to better growth rates, increased milk production, and enhanced overall health. Additionally, it regulates key reproductive hormones like estrogen and progesterone, which are essential for successful conception and pregnancy. Understanding the role of gut microbiota offers valuable insights for optimizing breeding and improving production outcomes, contributing to advancements in agriculture and veterinary medicine. This study emphasizes the critical ecological roles of mammalian microbiota, highlighting their essential contributions to health, productivity, and reproductive success. By integrating human and veterinary perspectives, it demonstrates how microbial communities enhance immune function, metabolic processes, and hormonal regulation across species, offering insights that benefit both clinical and agricultural advancements.

Neurodevelopmental Process Monitoring of Cytosine Arabinoside-Exposed Neurons Using Raman Spectroscopy.

Raman spectroscopy is used to monitor the development of live neurons exposed to cytosine arabinoside (ara-C). Ara-C is widely used to culture neurons and exclude non-neuronal cells. In this study, Raman spectra obtained from neurons exposed to ara-C were plotted using an analytical model of neuronal development to evaluate the impact of ara-C on neuronal development. After two days of culturing, neurons were exposed to ara-C for 24 h at final concentrations of 0 (control), 5, and 25 μM. Principal component analysis (PCA) was performed to build an analytical model for evaluating neurodevelopmental disorders caused by ara-C treatment. We projected the Raman spectra obtained from ara-C-treated cells onto the control group dataset. The distribution of PC1 scores for neurons exposed to ara-C at a final concentration of 5 μM was not significantly different from that of the control group. In contrast, under a final concentration of 25 μM, the data population at 10 and 15 days of culturing overlapped significantly with that of neurons at 4 days of normal culturing. These results suggest that Raman spectroscopy can detect very small physiological alterations in the neurons even after a short-term exposure (24 h) of ara-C. Our analytical method has high potential to evaluate the developmental stages for living neurons under exposure to chemicals.