暂无摘要。

GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily of the GPCR superfamily, which is the largest family of membrane protein receptors in the human genome. Studies in recent years have demonstrated that GPR56 is integral to the normal development of the brain and functions as an important player in cortical development, suggesting that GPR56 is involved in many physiological processes. Indeed, aberrant expression of GPR56 has been implicated in multiple neurological and psychiatric disorders, including bilateral frontoparietal polymicrogyria (BFPP), depression and epilepsy. In a recent study, it was found that upregulated expression of GPR56 reduced depressive-like behaviours in an animal model of depression, indicating that GPR56 plays an important role in the antidepressant response. Given the link of GPR56 with the antidepressant response, the function of GPR56 has become a focus of research. Although GPR56 may be a potential target for the development of antidepressants, the underlying molecular mechanisms remain largely unknown. Therefore in this review, we will summarize the latest findings of GPR56 function in neurological and psychiatric disorders (depression, epilepsy, autism, and BFPP) and emphasize the mechanisms of GPR56 in activation and signalling in those conditions. After reviewing several studies, attributing to its significant biological functions and exceptionally long extracellular N-terminus that interacts with multiple ligands, we draw a conclusion that GPR56 may serve as an important drug target for neuropsychological diseases.

OBJECTIVE: Music therapy (MT) is proposed to enrich the acoustic environment of very preterm infants (VPT) on the neonatal intensive care unit during a vulnerable period of brain development. The objective of this study was to investigate the effect of MT on the white matter (WM) microstructure. It is hypothesized that MT affects WM integrity in VPT.
METHODS: Randomized controlled trial enrolling infants born <32 weeks\' gestation. Infants were randomized to MT or standard care. Live MT was provided twice weekly from the second postnatal week onwards by a trained music therapist. At term equivalent age, participants underwent a cranial magnetic resonance imaging scan including sequences for diffusion tensor imaging analysis. Differences in WM microstructure were assessed using tract based spatial statistics with fractional anisotropy.
RESULTS: Of 80 infants enrolled, 42 were eligible for diffusion tensor imaging analysis (MT: n = 22, standard care: n = 20). While primary tract based spatial statistics analysis revealed no significant differences between groups, post hoc analysis with uncorrected p-values and a significance threshold of p < 0.01 revealed significant fractional anisotropy differences in several WM tracts including the bilateral superior longitudinal fasciculus, the left forceps minor and left fasciculus uncinatus, the corpus callosum, the left external capsule, and the right corticospinal tract.
CONCLUSIONS: Post hoc analysis results suggest an effect of MT on WM integrity in VPT. Larger studies including long-term outcome are necessary to confirm these effects of MT on WM microstructure and to assess its impact on clinical neurodevelopment.
BACKGROUND: Clinical trial number DRKS00025753.

Understanding health risks from methylmercury (MeHg) exposure is complicated by its link to fish consumption which may confound or modify toxicities. One solution is to include fish intake and a biomarker of MeHg exposure in the same model, but resulting estimates do not reflect the independent impact of accumulated MeHg or fish exposures. In fish-eating populations, this can be addressed by separating MeHg exposure into fish intake and average Hg content of the consumed fish. We assessed the joint association of prenatal MeHg exposure (maternal hair Hg) and fish intake (among fish-eating mothers) with neurodevelopment in 361 eight-year-olds from the New Bedford Cohort (born 1993-1998). Neurodevelopmental assessments used standardized tests of IQ, language, memory, and attention. Covariate-adjusted regression assessed the association of maternal fish consumption, stratified by tertiles of estimated average fish Hg, with neurodevelopment. Associations between maternal fish intake and child outcomes were generally beneficial for those in the lowest average fish Hg tertile, but detrimental in the highest average fish Hg tertile where, for example, each serving of fish was associated with 1.3 fewer correct responses (95% CI: -2.2, -0.4) on the Boston Naming test. Standard analyses showed no outcome associations with hair Hg or fish intake.

BACKGROUND: Community water fluoridation is an effective public health strategy for preventing dental caries, yet. Concerns exist about potential health problems. This study explores associations between tap water fluoride levels and pediatric disease burden, as well as neurodevelopmental outcomes at 6 years of age.
METHODS: This nationwide population-based cohort study included children born in Korean cities with and without tap water fluoridation projects, between 2006 and 2012, aiming for a fluoride concentration of 0.8 ± 0.2 mg/L in treated tap water. Data from the National Health Insurance Service were used, spanning from birth to 2018. The relationship between exposure to fluoridated tap water and incidence of 16 childhood diseases that were previously identified as potentially linked to fluoride exposure were examined. Additionally, we evaluated the neurodevelopmental outcomes across various domains, including gross motor, fine motor, cognition, language, social skills, and self-help functions. These assessments were performed using data from a comprehensive national health screening program for children aged six years.
RESULTS: A fluoride-unexposed group included 22,881 children, whereas a fluoride-exposed group comprised 29,991 children (52% males). Children in the fluoride-exposed group had a decreased risk of dental caries and bone fractures [hazard ratio (95% confidence interval, CI), 0.76 (0.63-0.93) and 0.89 (0.82-0.93), respectively] and increased risk of hepatic failures [1.85, (1.14-2.98)] compared to those in the unexposed group. Additionally, the risk ratio of abnormal neurodevelopmental screening outcomes increased by 9%, but this was statistically uncertain (95% CI, 0.95-1.26).
CONCLUSIONS: Fluoridated tap water was associated with an increased risk of hepatic failure but a decreased risk of bone fractures in children. The association between fluoridated tap water and neurodevelopmental screening outcomes at 6 years remains unclear, highlighting the need for further studies to clarify this association.

Critically ill newborns experience numerous painful procedures as part of lifesaving care in the Neonatal Intensive Care Unit. However, painful exposures in the neonatal period have been associated with alterations in brain maturation and poorer neurodevelopmental outcomes in childhood. The most frequently used medications for pain and sedation in the NICU are opioids, benzodiazepines and sucrose; these have also been associated with abnormalities in brain maturation and neurodevelopment making it challenging to know what the best approach is to treat neonatal pain. This article provides clinicians with an overview of how neonatal exposure to pain as well as analgesic and sedative medications impact brain maturation and neurodevelopmental outcomes in critically ill infants. We also highlight areas in need of future research to develop standardized neonatal pain monitoring and management strategies.

UNASSIGNED: Human cerebral organoids (hCOs) derived from pluripotent stem cells are very promising for the study of neurodevelopment and the investigation of the healthy or diseased brain. To help establish hCOs as a powerful research model, it is essential to perform the morphological characterization of their cellular components in depth.
UNASSIGNED: In this study, we analyzed the cell types consisting of hCOs after culturing for 45 days using immunofluorescence and reverse transcriptase qualitative polymerase chain reaction (RT-qPCR) assays. We also analyzed their subcellular morphological characteristics by transmission electron microscopy (TEM).
UNASSIGNED: Our results show the development of proliferative zones to be remarkably similar to those found in human brain development with cells having a polarized structure surrounding a central cavity with tight junctions and cilia. In addition, we describe the presence of immature and mature migrating neurons, astrocytes, oligodendrocyte precursor cells, and microglia-like cells.
UNASSIGNED: The ultrastructural characterization presented in this study provides valuable information on the structural development and morphology of the hCO, and this information is of general interest for future research on the mechanisms that alter the cell structure or function of hCOs.

Ageing is a continuous process that can cause neurodevelopmental changes in the body. Several studies have examined its effects, but few have focused on how time affects biological processes in the early stages of brain development. As studying the changes that occur in the early stages of life is important to prevent age-related neurological and psychiatric disorders, we aim to focus on these changes. The transcriptomic markers of ageing that are common to the analysed brain regions of C57Bl/6J mice were identified after conducting two-way ANOVA tests and effect size analysis on the time courses of gene expression profiles in various mouse brain regions. A total of 16,374 genes (59.9%) significantly changed their expression level, among which 7600 (27.8%) demonstrated tissue-dependent differences only, and 1823 (6.7%) displayed time-dependent and tissue-independent responses. Focusing on genes with at least a large effect size gives the list of potential biomarkers 12,332 (45.1%) and 1670 (6.1%) genes, respectively. There were 305 genes that exhibited similar significant time response trends (independently of the brain region). Samples from an 11-day-old mouse embryo validated the identified early-stage brain ageing markers. The overall functional analysis revealed tRNA and rRNA processing in the mitochondrion and contact activation system (CAS), as well as the kallikrein/kinin system (KKS), together with clotting cascade and defective factor F9 activation being affected by ageing. Most ageing-related pathways were significantly enriched, especially those that are strongly connected to development processes and neurodegenerative diseases.

OBJECTIVE: An update on the plasticity of the brain networks involved in autism (autism spectrum disorders [ASD]), and the increasing role of their synapses and primary non-motile cilia.
METHODS: Data from PubMed and Google on this subject, published until February 2024, were analyzed.
RESULTS: Structural and functional brain characteristics and genetic particularities involving synapses and cilia that modify neuronal circuits are observed in ASD, such as reduced pruning of dendrites, minicolumnar pathology, or persistence of connections usually doomed to disappear. Proteins involved in synapse functions (such as neuroligins and neurexins), in the postsynaptic architectural scaffolding (such as Shank proteins) or in cilia functions (such as IFT-independent kinesins) are often abnormal. There is an increase in glutaminergic transmission and a decrease in GABA inhibition. ASD may occur in genetic ciliopathies. The means of modulating these specificities, when deemed useful, are described.
CONCLUSIONS: The wide range of clinical manifestations of ASD is strongly associated with abnormalities in the morphology, functions, and plasticity of brain networks, involving their synapses and non-motile cilia. Their modulation offers important research perspectives on treatments when needed, especially since brain plasticity persists much later than previously thought. Improved early detection of ASD and additional studies on synapses and primary cilia are needed.

Maternal gestational obesity is related to risk of obesity in the child. This risk may be in part mediated by altered child temperament, which can affect mother-child interactions, including feeding and soothing behaviors that affect obesity risk. Our objective was to examine the association between maternal pre-pregnancy BMI and child zBMI and determine if child temperament, specifically positive Affectivity/Surgency, mediates this association. Using conditional process modeling, we analyzed data from 408 mother-child dyads enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Child temperament was assessed at 3 years of age via a parent report measure, the Child Behavior Questionnaire (CBQ), and child zBMI was calculated from in-person measurements of child height and weight at 4-5 years of age. Bivariate correlations showed that there was a significant positive correlation between zBMI and Surgency (r = 0.11, p = 0.03), and zBMI was also correlated with maternal pre-pregnancy BMI (r = 0.12, p = 0.02). Multivariable regression revealed that maternal pre-pregnancy BMI (adjusted β = 0.15, 95% confidence interval [CI]; 0.00-0.05, p = 0.02) and Surgency scores (adjusted β = 0.14, 95% CI; 0.02-0.28, p = 0.03) were associated with higher child zBMI at 4-5 years of age. Mediation analysis showed that Surgency mediated the association between pre-pregnancy BMI and child zBMI. Our models controlled for maternal gestational weight gain, gestational diabetes, socioeconomic status, maternal anxiety and depression, and gestational age at birth. Overall, maternal pre-pregnancy BMI was positively associated with child zBMI, and this association was mediated by higher child Surgency scores.