International Journal of Developmental Neuroscience最新文献

Variants of the CNTNAP2 gene are closely associated with various neurological disorders, including neurodevelopmental disorders, schizophrenia and behavioural abnormalities. Biallelic CNTNAP2 gene variants may lead to more complex or severe neurodevelopmental phenotypes; however, due to a lack of sufficient reports, especially regarding prenatal manifestations, the relationship between CASPR2-deficiency neurodevelopmental disorder and genotype remains unclear. Herein, we report the case of a child with neurodevelopmental disorder who presented with a dysplastic corpus callosum on prenatal ultrasound. The proband experienced seizures, delayed growth and development and autism after birth. This prompted whole-exome sequencing of the family, which revealed that the proband had compound heterozygous variants in the CNTNAP2 gene. Variant 1 was NM_014141.6:c.551-2A > T, inherited from his father, and Variant 2 was loss1 (EXON:2–3), inherited from his mother. We constructed a plasmid for Variant 1 and performed a minigene experiment, which revealed that the variant was a frameshift variant that resulted in a truncated protein, p.Trp184TyrfsTer7. Our findings suggest that biallelic CNTNAP2 gene variants may affect brain development during the foetal period, and physicians should be vigilant for CNTNAP2 gene variants in cases of agenesis of the corpus callosum or cortical dysplasia.

The clinical diagnostic parameters of dyslexia and the alterations it creates on brain connectivity continue to be the focus of current studies. In this study, where clinical neuropsychiatric tests and neuroimaging results are examined together, it is aimed to examine the functional connectivity differences that occur in the brain regions related to the reading pathway in children with dyslexia in a resting state and task-based manner and to compare them with healthy controls. Correlation analyses were performed to evaluate the correlation between the resting state and the reading task of the groups with age, word reading count and WISC-4 score and mean brain activity. The findings indicate that dyslexia is linked to deficits in the phonological component and that the correlation between intelligence and reading speed is lower in the dyslexia group than in healthy controls. It has also been observed that children with dyslexia have difficulties in the development of phonological input, semantics and phonological output, independent of intelligence and that neuronal connections are affected in a similar way. These findings contribute to the functional differences detected in dyslexia by neuroimaging, and may help to understand the complex nature of dyslexia and to make educational and therapeutic methods more effective.

Microglia, the resident macrophages of the central nervous system, are a diverse population that develop during embryonic and postnatal stages in the mouse. Several signalling pathways are involved in their specification and maturation, but other types of cues might be involved, including lipid metabolism. Here, we evaluated the effect of the inactivation of two main cholesterol transporters in mice, ABCA1 and SR-B1, on microglial development. Using public datasets, we showed that both transporters are expressed in microglia and are differentially regulated in neurodegeneration models. Inactivation of either transporter was associated with distinct effects on microglial density and/or morphology at different developmental stages and in different brain regions. These studies suggest that microglia require appropriate lipid transport to support their homeostatic identity and could implicate this process in neurodegenerative diseases.

This study investigated the effect of sericin consumption during gestation on the neurodevelopmental reflexes, motor behaviour and biochemical profiles of mice offspring. Forty pregnant NMRI mice were randomly assigned into four groups: a control group and three experimental groups that received sericin (112.5, 225 and 450 mg/kg) via oral administration on Days 5, 8, 11, 14 and 17 of gestation. Then, neurodevelopmental reflex tests included ambulation, hindlimb foot angle, hindlimb suspension, surface righting, front-limb suspension, grip strength and negative geotaxis were assessed. Additionally, blood samples were collected to evaluate biochemical parameters, including serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), growth hormone (GH) and insulin-like growth factor (IGF) levels. The findings revealed that prenatal sericin exposure improved ambulation scores, reduced hindlimb foot angle and increased hindlimb suspension scores (p < 0.05). Sericin administration led to an increase in grip strength and front-limb suspension scores (p < 0.05). Furthermore, sericin administration decreased serum and brain MDA levels while increasing serum and brain SOD, GPx and TAC levels (p < 0.05). Sericin exposure also increased serum GH and IGF levels (p < 0.05). The results indicated that maternal sericin consumption during gestation had a positive impact on offspring's motor skills and antioxidant status.

Zebrafish (Danio rerio) have emerged as a pivotal model organism in translational neuroscience, neuropharmacology and CNS disorder research, leveraging their striking anatomical and physiological parallels to humans. With a brain architecture and functional pathways that are closely similar to those of humans, zebrafish enable critical insights into brain development, neuro-circuitry and disease mechanisms. Notably, zebrafish have a number of benefits over more conventional mammalian models like mice and rats, including their rapid development, optical transparency allowing for real-time imaging and capacity to perform high-throughput genetic and pharmacological screens inexpensively. The combination of vertebrate complexity and experimental tractability that zebrafish possesses renders them uniquely placed for large-scale investigations of brain function and disease. This review synthesizes recent advancements in utilizing zebrafish to model brain disorders such as depression, anxiety, psychoses, autism spectrum disorders, cognitive impairments and drug-induced neurobehavioural alterations. By integrating findings from genetic, pharmacological and behavioural studies, we underscore zebrafish's unique advantages, including genetic tractability, cost-efficiency, high-throughput screening capacity and conserved neuroendocrine and behavioural responses. These features facilitate the exploration of complex neuropsychological processes and drug–brain interactions, bridging gaps between molecular mechanisms and behavioural outcomes. Zebrafish models have proven instrumental in unravelling the neurobiological underpinnings of human psychiatric and neurological disorders, offering a versatile platform for studying gene–environment interactions, neurodevelopmental trajectories and pharmacological interventions. Their translational relevance is further enhanced by rapid developmental cycles, optical transparency during early stages and robust behavioural assays that capture nuanced phenotypes. This review highlights the transformative role of zebrafish in accelerating drug discovery, optimizing neuropharmacological screening and advancing personalized therapeutic strategies. By consolidating evidence from diverse studies, we highlight zebrafish's capacity to address fundamental questions in neuroscience while fostering innovative approaches to diagnose, treat and prevent brain disorders, ultimately driving progress towards precision medicine in neurology and psychiatry.