Developmental Neuroscience最新文献

Introduction: According to literature, early stress may lead to a higher susceptibility to the action of various stressors later in life, thus largely contributing to the development of a wide range of affective disorders. Disrupting maternal care is one way to destabilize the environment for pups, which may result in the formation of an altered reaction to acute or moderate stress.

Methods: In this study, we analyzed the effects of limited bedding and nesting material (LBN) in PND2-PND9 on baseline gene expression in the hippocampus and frontal cortex of 1-month old rats and the expression of the same genes under conditions of 60-minute restraint. Among the analyzed genes, some were associated with glucocorticoids (Nr3c1 and Nr3c2), others with the activation of the immune system (Nfkbia, Ccl2, Il1b, Il6, Tnfα, Cx3cl1, Cx3cr1, and Ncf1), and yet others with the activation of neuronal networks under stress (Cfos, Ier-2). Gene expression was assessed using real-time PCR (RT-PCR).

Results: Exposure to LBN during early postnatal life significantly increased baseline expression of the Fos gene in the amygdala of adolescent rats. LBN exposure more slightly affected the expression of other analyzed genes (Nr3c1, Cx3cl1, Ier2, Ncf1) or evoked alterations of their expression in this group only after exposure to acute restraint stress. The hyperglycemic response to acute restraint was attenuated in LBN-exposed animals, while corticosterone levels were comparable to controls. Among the studied genes, the expression of Nfkbia, Il6, and Tnf was primarily influenced by acute restraint stress, independently of LBN history. The amygdala and ventral hippocampus were the brain regions where the expression of the analyzed genes appeared most sensitive to the experimental manipulations.

Conclusion: These data indicate that early-life stress induced by LBN leads to a sustained increase in baseline Fos expression in the amygdala and alters the metabolic response to acute stress in adolescence. The findings further suggest that the amygdala and ventral hippocampus are key regions where the expression of a limited set of stress-related genes is modulated by the interplay of early-life adversity and acute stress. This points to a potential role for amygdalar circuits in the altered stress reactivity observed following adverse early-life conditions.

Introduction: Neonatal rats, but not juvenile rats, show spontaneous hindlimb locomotor recovery after complete thoracic spinal cord transection (SCT). Significant increases in parvalbumin-positive proprioceptive nerve terminals are observed on motoneurons in both neonatal and juvenile rats with SCT compared with intact rats.

Methods: In the present study, we focused on Chx10-positive V2a interneurons, which partially comprise the central pattern generator, and examined parvalbumin-positive nerve terminals on Chx10 neurons and the perineuronal net formation around these neurons using Wisteria Floribunda agglutinin (WFA) as a marker 2 weeks after SCT on postnatal day 5 (neonatal) or day 20 (juvenile).

Results: Rats with CST during the neonatal period had a significantly greater number of parvalbumin-positive terminals on Chx10 neurons compared to age-matched intact rats, whereas no significant difference was detected between rats with SCT during the juvenile period and age-matched intact rats. Chx10 neurons for which ≥50% of the circumference was surrounded by WFA were identified as WFA-positive. The proportion of WFA-positive neurons among Chx10-positive neurons did not differ significantly between neonatal SCT and age-matched intact rats, but was significantly higher in juvenile SCT and age-matched intact rats.

Conclusion: These findings suggest that SCT promotes the formation of proprioceptive afferent terminals on Chx10-positive neurons. The significant increase in terminals following SCT in neonatal rats might facilitate spontaneous motor recovery, whereas enhanced perineuronal net formation around Chx10 neurons following juvenile SCT might restrict synaptic formation and impair motor recovery.

Background: The proper functioning of the central nervous system depends on the cooperation of distinct neuronal subtypes generated during development.

Summary: Here, we review new insights provided by recent research and technological advances into the mechanisms underlying the generation of the remarkable diversity of inhibitory GABAergic neurons (INs). INs are generated in the ventral telencephalon or subpallium and migrate long distances to populate multiple brain regions. INs exhibit considerable morphological, molecular, and electrophysiological diversity. This diversity is mediated by intrinsic and extrinsic factors, including secreted molecules (such as sonic hedgehog).

Key messages: This review examines the role of extrinsic factors in the establishment of distinct subpallial domains and the subsequent emergence of IN diversity. We begin by summarizing the in vivo morphogenesis of this process and then highlight the new technologies that allow us to revisit the role of morphogens in subpallial development and IN specification.

In the article by Zhou et al. entitled "Caffeine as a Treatment for Perinatal Hypoxic-Ischemic Brain Injury: The Potential Risks and Benefits" [Dev Neurosci. 2025; DOI: 10.1159/000545126] the license was incorrect, and it has changed from CC BY-NC 4.0 to CC BY 4.0.The original article has been updated.

In the article by Vancolen et al. entitled "Androgen Aggravates Chorioamnionitis-Induced White Matter Brain Injury and Neurobehavioral Impairments in Males" [Dev Neurosci. 2025; DOI: 10.1159/000545074] the license was incorrect, and it has changed from CC BY-NC 4.0 to CC BY 4.0.The original article has been updated.

Background: Branched chain amino acid (BCAA) metabolism plays roles in various cellular processes, including energy homeostasis, anabolic signaling, and production of glutamate, the primary excitatory neurotransmitter. Emerging evidence also suggests BCAA metabolism has relationships to inflammatory and hypoxic cellular responses. Recent work in adult and adolescent clinical populations has suggested that BCAA dietary supplementation may improve outcomes associated with traumatic brain injury. Given these links, examining the putative mechanisms and potential therapeutic applications of modulating dietary BCAA content in the context of inflammatory and hypoxic developmental brain injury may reveal mechanisms for intervention in affected infants.

Summary: Inflammatory and hypoxic brain injuries influence the dynamics of BCAA metabolism in the fetal brain. Inflammatory insults to the developing brain may increase BCAA catabolism downstream of the branched chain ketoacids (BCKAs). The effect of altered BCAA metabolism on the pathophysiology of inflammatory developmental brain injury is currently unclear but may play a role in microglial response. Hypoxic brain injury seems to increase BCAA concentration in the fetal brain, possibly because of re-amination of BCKAs to the parent BCAAs, or via increased protein breakdown during hypoxia.

Key messages: The apparent relationship between aberrant BCAA metabolism and inflammation or hypoxia warrants consideration of BCAA supplementation or restriction as a strategy for attenuating developmental brain injury that is associated with these pathologic events. This approach could entail alterations of maternal diet during pregnancy or the feeding of infant formula that is fortified with or restricted in BCAA. These types of interventions have been safely and effectively employed in cases of inborn errors of BCAA metabolism, suggesting feasibility in infant populations. Both in vitro and preclinical work is necessary to elucidate how BCAA supplementation or restriction may affect the sequelae of inflammatory and hypoxic developmental brain injury.

Introduction: Group B Streptococcus (GBS) colonization leads to placental infection and inflammation, known as chorioamnionitis (CA). Fetal exposure to CA is linked to elevated risks of neurobehavioral impairments in offspring, including autism spectrum disorder, which is more prominent in males than females. In our preclinical model of GBS-induced CA, males exhibited heightened placental inflammation compared to females, correlating with more severe subsequent neurobehavioral impairments. We hypothesize that androgens upregulate the placental immune response in male fetuses, potentially contributing to GBS-induced autistic-like traits in male offspring. Our previous findings demonstrated that there were reduced pro-inflammatory cytokines and polymorphonuclear cell infiltration in flutamide (androgen receptor antagonist) plus GBS-infected compared to vehicle plus GBS-infected placenta. In this study, we investigated the effect of end gestational androgen blockade on brain injury patterns and neurobehavioral outcomes in offspring in utero exposed to GBS CA.

Methods: Lewis dams received daily injections of vehicle or flutamide from gestational day (G) 18-21, followed by saline or inactivated GBS injections from G19 to 21. Behavioral assessments were conducted from postnatal day (P) 9-40 and brains were dissected on P50.

Results: Behavioral assessments revealed impaired social interactions in CA-exposed versus unexposed male rats. These impairments were not observed in flutamide-treated rats. Histological analysis of forebrains at P50 showed lateral forebrain ventricle enlargement and reduced periventricular white matter thickness, namely the corpus callosum and external capsule in offspring exposed to CA contrasting with an improvement in these outcomes observed in flutamide treated rats. Exposure to CA reduced the density of CC-1+ oligodendrocytes in the external capsule whereas flutamide mitigated this reduction in offspring at P50.

Conclusion: These findings suggest a significant role for androgens in the skewed sex ratio observed in developmental impairments resulting from perinatal inflammation, underscoring the need for personalized sex-specific neuroprotective therapies.

Introduction: Perinatal stroke causes lasting neurological deficits and there are currently no effective treatment options. Established animal models of perinatal stroke do not always mimic the clinical presentation of neonatal injury or are technically challenging to perform. The photothrombotic (PT) stroke model is a minimally invasive method that replicates focal ischaemic injury. Few studies have applied the PT model in neonatal contexts, and none have examined both short- and long-term effects across varying injury severities. This study aimed to optimize a protocol to create a mild model of perinatal stroke and subsequently characterize injury progression, neuropathological impact, and motor deficits over time.

Methods: On postnatal day 10 we used the PT method to induce perinatal stroke in rat pups. Pups were exposed to various light exposure times (10, 20, or 30 min) to determine the optimal time needed to produce a mild and reproducible cortical stroke injury. Behavioural assessments were conducted on days 4, 10, 20, and 30 post-injury. Brains were collected for analysis on days 3 and 40 post-injury.

Results: Three days post-injury, the 20 and 30 min group had significant focal lesions and microbleeds were present in each of the PT groups. All PT groups showed significant neuron loss in the peri-infarct region and the thalamus, and microglia activation in multiple brain regions. As 30 min of light exposure showed extensive cortical tissue loss (>70%), we excluded the 30-min group from long-term assessment. 40 days post-injury, the 10 and 20 min groups demonstrated significant tissue loss and neuronal loss in the peri-infarct region and thalamus, but only the 20 min group showed neuron loss in the hippocampus. The 10 and 20 min groups both demonstrated ongoing motor deficits.

Conclusion: Our results demonstrate that increasing light exposure time in PT stroke results in a more severe stroke phenotype. 30 min of light exposure resulted in a severe injury at only 3 days post insult, therefore, was not further investigated. 10 and 20 min of light exposure had a similar effect at 3 days, however, after 40 days the 20 min exposure time created a moderate injury phenotype. From this study, we propose that 10 min of light exposure is optimal to create a mild stroke phenotype and is associated with motor deficits and altered neuropathology. This injury phenotype provides a focal and reproducible insult, while still being mild enough to feasibly test therapeutics.

Introduction: Prenatal alcohol exposure (PAE) can lead to a wide spectrum of deficits in growth and neurological function, and there is an established link between PAE and auditory dysfunction. However, the effects of PAE on auditory development are complex and vary depending on the age and pattern of alcohol exposure.

Methods: In this study, we developed a mouse model of PAE during the first half of the gestational period, mimicking alcohol consumption during the first trimester of pregnancy in humans.

Results: This exposure did not affect overall growth or induce anxiety-related symptoms in the offspring, as indicated by normal body weight change and largely unchanged behaviors in the open field and elevated zero maze tests. However, several aspects of auditory function were affected by PAE. Offspring born from prenatal alcohol-exposed dams displayed smaller auditory brainstem responses (ABRs) at 2-month-old as compared to those from control dams, suggesting weakened neuron synchronization within auditory brainstem circuits. Additionally, a reduction in the reproducibility of ABR peaks III/IV was observed in PAE offspring. In contrast, the overall hearing sensitivity and neuron transmission was not affected by PAE, as evaluated by ABR thresholds or peak latencies. In an acoustic startle test, PAE offspring failed to display prepulse inhibition to low levels of prepulses more frequently than control offspring at both 2 weeks old and 2 months old, suggesting an early-onset and lasting deficit in auditory gating or sound level differentiation.

Conclusion: These results demonstrate that mice exposed to alcohol during early gestation have largely preserved auditory responses but show significant alterations in specific features of auditory processing.