International Journal of Developmental Neuroscience最新文献

Background: Maternal obesity is a risk factor for neurodevelopmental disorders in the offspring. In recent years, it has been suggested that not only maternal obesity but also dietary intake during pregnancy and lactation may influence children's behaviour and neurodevelopment. In the present study, we aimed to evaluate the effects of maternal high-fat diet (HFD) exposure during pregnancy and lactation on offspring locomotion and orexin neuronal activity in the lateral hypothalamus (LH).

Methods: Dams were fed either an HFD or a control diet (CD) during pregnancy and lactation. After weaning, their offspring were fed a CD. Male and female offspring were evaluated for behaviour at age 5 weeks using the open field test (OFT) and elevated plus maze (EPM) test. To investigate age-related effects, the same male offspring were further evaluated at age 5, 13 and 25 weeks using the OFT. Immunohistochemical staining was performed at age 5-6 weeks to quantify orexin A-positive neurons in the LH. Double staining for orexin A and c-Fos was conducted in the brains collected at 1-1.5 h after the OFT.

Results: In male offspring at age 5-6 weeks, the HFD group exhibited a significantly higher total distance in both the OFT and EPM compared with the CD group. The number of orexin A-positive neurons in the LH was higher in the HFD group than that in the CD group. However, significant differences were not observed in females. In the longitudinal assessment of male offspring, the total distance in the OFT significantly increased in the HFD group at age 5 and 13 weeks but showed no significant difference at age 25 weeks. Furthermore, double staining for orexin A and c-Fos in 5- to 6-week-old male offspring revealed significantly higher co-localisation in the HFD group than in the CD group.

Conclusions: Maternal HFD exposure during pregnancy and lactation increases locomotor and orexin neuronal activity in male offspring; however, these effects diminish with age. These results suggest that a short duration of maternal HFD exposure may enhance locomotor activity in male offspring, especially juveniles, via the alteration of orexin neuronal activity in the LH.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by deficits in social interaction, communication and repetitive behaviours. Emerging evidence implicates dysfunction in γ-aminobutyric acid (GABA) signalling, the brain's primary inhibitory neurotransmitter system, in the pathogenesis of ASD. GABAergic neurotransmission plays a pivotal role in neurodevelopment, particularly in balancing excitatory and inhibitory signalling, synaptic plasticity and neural circuit maturation. Dysregulation in GABA synthesis, receptor expression and transport has been observed in both clinical and preclinical models of ASD, leading to disrupted neuronal connectivity and atypical behavioural phenotypes. This review critically explores the alterations in GABAergic signalling in ASD, highlighting the role of various GABA receptor subtypes (GABA_AR, GABA_BR and GABA_CR) and associated transport and metabolic enzymes. The therapeutic implications of modulating GABAergic activity are also examined. Pharmacological agents, such as GABA receptor agonists, GABA reuptake inhibitors and GABA transaminase inhibitors, exhibit varied efficacy profiles. Among these, GABAB receptor agonists, including arbaclofen and baclofen, show the most promise in improving social behaviour and reducing core ASD symptoms. Conversely, some agents that elevate GABA levels, such as vigabatrin and valproic acid, may exacerbate ASD-like features under certain conditions. Collectively, the data suggest that targeted modulation of GABAergic pathways, particularly GABA_B receptor signalling, offers a viable avenue for therapeutic intervention in ASD. However, further mechanistic studies and well-designed clinical trials are required to elucidate the optimal strategies for harnessing GABA modulation in ASD management.

Objectives: Autism spectrum disorder (ASD) is an increasingly occurring neurobiological condition. As a main risk factor, maternal separation (MS) stress has a role in the foundation of ASD. Simvastatin possessed neuroprotective effects. We intended to estimate the impact of simvastatin on autism-related behaviours in mice subjected to the MS paradigm, concentrating on its likely effects on hippocampal oxidative stress imbalance and neuroinflammation.

Methods: Forty mice were unintentionally assigned into 5 groups: including control group (normal saline treated [10 mL/kg]) and MS groups respectively administrated with normal saline (10 mL/kg) or simvastatin at doses of 2.5, 5 and 10 mg/kg for 2 weeks. Shuttle box, marble burying (MB) and three-chamber sociability trials were performed. Hippocampal malondialdehyde (MDA), nitrite, total antioxidant capacity (TAC) and expression of proinflammatory cytokines, counting TLR4, TNF-α, IL-1β and NLRP3, were measured.

Results: Simvastatin in MS mice led to notable improvements in behaviour and cognition as elevating social interaction indices in the three-chamber test, enhancing passive avoidance memory in the shuttle box test and reducing repetitive actions as observed in the marble burying test. Simvastatin abridged the hippocampal nitrite content and neuroinflammatory response.

Conclusions: Simvastatin, perhaps through weakening the hippocampal nitrite imbalance and neuroinflammation, alleviated autism-related behaviours in MS mice.

Background: This study examined cingulin and interleukin-6 (IL-6) levels in children with specific learning disorder (SLD) to explore their association with inflammation and tight junction-related barrier biological processes in the context of the disorder.

Methods: The research compared 40 children with SLD and 41 healthy peers using a cross-sectional, case-controlled design. Serum cingulin and IL-6 levels were measured using the ELISA method. The Mathematics, Reading and Writing Assessment Scale (MOYA) teacher and parent forms were applied to evaluate disease severity in the SLD group.

Results: Both cingulin and IL-6 levels were significantly higher in the SLD group than in the controls (p = 0.005 and p = 0.009, respectively). These differences maintained their significance during covariance analysis. These findings indicate a significant group-related difference in cingulin and IL-6 levels, and that this was independent of age, gender and body mass index. A positive correlation was determined between cingulin and IL-6 in the SLD group (r = 0.472, p = 0.020). In the context of logistic regression analysis, cingulin demonstrated an independent association with the presence of SLD (OR = 1.006, p = 0.041), while IL-6 did not. An AUC value of 0.679 was calculated for cingulin at receiver operating characteristic analysis (p = 0.003).

Conclusion: Elevated serum cingulin and IL-6 levels in children with SLD may reflect inflammatory activity and barrier-related biological processes associated with the disorder. These findings should be interpreted as preliminary and require confirmation in larger, longitudinal studies incorporating direct assessments of barrier function.

Early postnatal ethanol exposure (PNEE) and early-life stress (ELS) are major contributors to persistent deficits in cognition, motivation and emotional regulation. These insults disrupt hippocampal plasticity and increase vulnerability to psychiatric disorders. Vitamin D (VitD), a neuroactive steroid, has emerged as a potential modulator of neurodevelopment and plasticity. We investigated whether adolescent VitD supplementation could mitigate behavioural and neuroplastic impairments resulting from early exposure to ethanol and maternal separation. On postnatal day (PND) 2, 64 Wistar rat pups (male and female) were randomized into eight experimental groups (n = 8 animals per group, with sex balanced across groups): (1) control, (2) VitD, (3) ethanol (EtOH), (4) EtOH + VitD, (5) maternal separation (MS), (6) MS + VitD, (7) EtOH + MS, and (8) EtOH + MS + VitD. EtOH groups received 5 g/kg i.p. ethanol on alternate days from PND 4-10. MS groups were separated from the dam for 3 h/day from PND 2-14. From PND 22-37, VitD groups received 1000 IU/kg/day of cholecalciferol. Behavioural assessments included palatable food intake and reward omission-based task. Brains were processed for doublecortin (DCX) immunohistochemistry and Golgi-Cox analysis. EtOH + MS animals displayed increased latency to eat, reduced food consumption and persistent feeder-directed responding following reward omission. VitD treatment reversed these effects, improving motivational performance and reducing reward omission-induced responding. VitD also restored hippocampal neurogenesis and normalized dendritic complexity and length. Vitamin D supplementation during adolescence mitigates behavioural and neuroplasticity deficits induced by PNEE (corresponding to the third trimester of human brain development) and ELS. These findings support VitD as a promising therapeutic strategy for neurodevelopmental disorders such as foetal alcohol spectrum disorder (FASD).

The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. However, it is also during this phase that the offspring are highly susceptible to changes triggered by maternal malnutrition, which can lead to deficiencies in brain development and affect behaviour throughout life. This study investigated the effects of maternal dietary restrictions, caloric restriction (CR) and intermittent fasting (IF), during lactation on the nutritional and developmental outcomes of Wistar rat dams and offspring (males and females) into adolescence. The litters (dam and eight pups) received the following dietary conditions: control, received the lab chow (Nuvilab CR-1) ad libitum (n = 8 litters); caloric restriction (CR), received 50% of the chow (Nuvilab CR-1) consumed by the control group (n = 8 litters); intermittent fasting (IF), received lab chow (Nuvilab CR-1) ad libitum for the first 24 h, followed by a 24-h period without access to food. This procedure was repeated throughout the entire lactation period. The study measured body weight, food and water intake, serum biochemistry parameters (glucose, cholesterol, triglycerides, bilirubin, ALT/AST and creatinine) and the redox state of the hypothalamus. In relation to the dams, CR and IF groups displayed a marked weight loss during lactation. Our findings show that CR and IF led to marked undernutrition in both male and female offspring, persistent through weaning into adolescence. Both groups showed a reduction in serum glucose levels in the offspring, as well as a reduction in the activity of superoxide dismutase (SOD) in the hypothalamus. This study highlights the profound impact of maternal nutrition during lactation on offspring nutrition, suggesting that restrictive diets may compromise offspring development and metabolic health.

Background: The HUWE1 gene plays a crucial role in mediating embryonic development as well as the differentiation and proliferation of neural cells. Variants in the HUWE1 are closely associated with intellectual developmental disorder. This study is designed to characterize the clinical phenotype of neurodevelopmental disorder in a cohort of seven children associated with variants in the HUWE1.

Methods: Blood samples of seven children with neurodevelopmental disorders and their parents were collected for trio whole exome sequencing. HUWE1 (NM_031407) variants were confirmed by Sanger sequencing.

Results: A total of 7 children were diagnosed as HUWE1-related neurodevelopmental disorder, involving three girls and four boys. All these HUWE1 variants were missense variants (four newly detected HUWE1 variant sites). This study suggested that HUWE1 variants posed varying influences on the facial features, height and speech, social and gross motor skills. Specifically, children with the p. Gly4310Arg variant presented malocclusion-associated chewing and swallowing difficulties.

Conclusion: Our findings further broaden the genotypic-phenotypic spectrum of HUWE1 variants and highlight the crucial role of the HECT domain in the pathogenicity of HUWE1 gene variants. Moreover, children with HUWE1 variants exhibited certain symptoms of attention-deficit/hyperactivity disorder (ADHD), social dysfunction and abnormal chewing function, which warrant further investigation.