International Journal of Developmental Neuroscience最新文献

Prenatal VPA exposure is used to model ASD-like symptoms. Disrupted empathy is frequently observed in individuals with ASD, but empathy-like behaviour is not well documented in animal models. Pregnant Wistar Albino rats were administered either 400 mg/kg VPA or saline i.p. on E12.5. Empathy-like behaviour was assessed at P30 and P60 in both female and male offspring, who were also tested for olfactory discrimination, sociability, locomotor activity, and pre-pulse inhibition. Prenatal exposure to VPA significantly impaired empathy-like behaviour, as measured by the duration of time the subject spent with its sibling and the frequency of attempts to open the restrainer door. When P30 and P60 results were compared within groups, a developmental arrest in empathy-like behaviour was observed in the VPA group, whereas the control group showed improvement in their scores. Prenatal exposure to VPA also resulted in significantly decreased sociability and pre-pulse inhibition rates. In this study, an adapted version for measuring empathy-like behaviour has been proposed. This version involved a restrained sibling and no prior training, allowing the measurement to be independent of learning, memory, and stranger anxiety. The results show that VPA has negative effects on social development and is a valid tool for modelling ASD in both females and males.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent social communication deficits and restricted, repetitive behaviours, with significant overlap in anxiety-related symptoms. Both genetic and environmental factors contribute to the development of ASD, with early-life stressors, such as maternal separation (MS), and exposure to neurotoxic agents, like valproic acid (VPA), being key environmental contributors. This study investigates the combined impact of maternal deprivation (MD) and postnatal VPA exposure on autism-like behaviours and neurodevelopmental outcomes in male and female rats. Rats exposed to MD from postnatal days 2 to 4 exhibited significant changes in social interaction and anxiety-like behaviours, with female rats being more sensitive to MD than males. Postnatal VPA exposure resulted in similar behavioural alterations, including increased anxiety and social impairment, aligning with previous findings of VPA-induced neurodevelopmental deficits. A combination of MD and VPA exposure exacerbated anxiety-like behaviours in females, indicating that early-life stress and environmental toxins can synergistically affect neurodevelopment. Our results further suggest that the impact of these exposures may differ between sexes, with females showing heightened sensitivity to both MD and VPA-induced stress. These findings provide valuable insights into the complex interactions between genetic, environmental and epigenetic factors in ASD pathophysiology. The study underscores the critical role of early-life stressors, such as MD, in exacerbating neurodevelopmental disorders, particularly when combined with neurotoxic environmental factors like VPA. The sex-specific differences observed in behavioural outcomes suggest the importance of considering biological sex in future ASD research and therapeutic strategies.

Foetal exposure to electromagnetic fields (EMFs) may cause marked neurocognitive impairment, although the mechanisms involved are still unclear. EMF induces region-specific neuronal and astroglial death in the rat hippocampus. Poly (ADP-ribose) polymerase-1 (PARP-1) regulates necrosis, apoptosis and other cellular processes occurring following injury. This study, therefore, investigated whether PARP-1 also regulates neuronal responses in the hippocampus of rats subjected to EMF radiation during different developmental periods. Male and female rats were first allowed to mate in separate cages. Rats identified as pregnant were then divided into four groups. A 900-MHz EMF was applied for 2 h daily on gestational days (GD) 1–7, GD 8–14 and GD 15–21. The female offspring were sacrificed at the end of the 28th postnatal day, and PARP-1 and Caspase-3 expressions in the hippocampus were then evaluated. No special treatment was applied to the control group. In the EMF-exposed group, pyramidal neurons in the cornu ammonis (CA) region appeared normal after exposure on GD 1–7 but were darkly stained and shrunken after exposure on GD 15–21, while the majority of granular cells exhibited a normal appearance during all GDs. The group exposed to EMF on GD 15–21 exhibited strong PARP-1 and Caspase-3 immune reactivity in CA and dentate gyrus (DG) cells. Higher H-scores were also observed in the EMF-exposed group following GD 15–21 irradiation. As a result, a 900-MHz EMF application at GD 15–21, which coincides with hippocampal neurogenesis, triggered hippocampal neuron cell death by activating PARP-1 and Caspase-3.

Contact between mother and child is essential for the proper development of an infant's physiological systems, brain maturation and behavioural outcomes. Early life stress (ELS), which includes factors such as inadequate parental care and childhood abuse, significantly increases the risk of developing neuropsychiatric disorders, including anxiety and depression. This review examines the impact of maternal separation (MS) on depression, anxiety and pain behaviour, with a particular emphasis on neuroinflammatory pathways. Experiences of ELS can adversely affect the maturation of neurotransmitter systems and associated neural circuits that are crucial for processing painful stimuli and regulating anxiety and depression. Stressful experiences trigger inflammatory processes in the brain, initiating immune responses in neural cells and stimulating the production of pro-inflammatory cytokines. In mammals, MS serves as a significant stressor that activates the hypothalamic–pituitary–adrenal (HPA) axis and other stress-related systems, leading to increased immune challenges and heightened pain sensitivity in adulthood due to systemic inflammation. Key inflammatory mediators, such as IL-1β, IL-6 and TNF-α, play critical roles in the development of pathological pain, while the activation of microglia releases inflammatory mediators that contribute to neurological dysfunction and the pathophysiology of stress, depression and anxiety. Moreover, therapeutics targeting oxidative stress and inflammation have shown promise in alleviating affective disorders following MS. This review discusses potential pathways, with a primary focus on neuroinflammatory mechanisms and the therapeutic strategies that may mitigate the adverse effects of MS. There is a pressing need for further research to elucidate the underlying pathways and identify effective interventions to improve mental health outcomes in individuals affected by MS.