Developmental Neuroscience最新文献

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.

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.

Introduction: Children with specific language impairment (SLI) have difficulties in different speech and language domains. Electrophysiological studies have documented that auditory processing in children with SLI is atypical and probably caused by delayed and abnormal auditory maturation. During the resting state, or different auditory tasks, children with SLI show low or high beta spectral power, which could be a clinical correlate for investigating brain rhythms.

Methods: The aim of this study was to examine the electrophysiological cortical activity of the beta rhythm while listening to words and nonwords in children with SLI in comparison to typical development (TD) children. The participants were 50 children with SLI, aged 4 and 5 years, and 50 age matched TD children. The children were divided into two subgroups according to age: (1) children 4 years of age; (2) children 5 years of age.

Results: The older group differed from the younger group in beta auditory processing, with increased values of beta spectral power in the right frontal, temporal, and parietal regions. In addition, children with SLI have higher beta spectral power than TD children in the bilateral temporal regions.

Conclusion: Complex beta auditory activation in TD and SLI children indicates the presence of early changes in functional brain connectivity.

Introduction: Children with specific language impairment (SLI) have difficulties in different speech and language domains. Electrophysiological studies have documented that auditory processing in children with SLI is atypical and probably caused by delayed and abnormal auditory maturation. During the resting state, or different auditory tasks, children with SLI show low or high beta spectral power, which could be a clinical correlate for investigating brain rhythms.

Methods: The aim of this study was to examine the electrophysiological cortical activity of the beta rhythm while listening to words and nonwords in children with SLI in comparison to typical development (TD) children. The participants were 50 children with SLI, aged 4 and 5 years, and 50 age matched TD children. The children were divided into two subgroups according to age: (1) children 4 years of age; (2) children 5 years of age.

Results: The older group differed from the younger group in beta auditory processing, with increased values of beta spectral power in the right frontal, temporal, and parietal regions. In addition, children with SLI have higher beta spectral power than TD children in the bilateral temporal regions.

Conclusion: Complex beta auditory activation in TD and SLI children indicates the presence of early changes in functional brain connectivity.

Introduction: Upstream stimulating factor 2 (USF2) belongs to basic Helix-Loop-Helix-Leucine zipper transcription factor family, regulating expression of genes involved in immune response or energy metabolism network. Role of USF2 in neuropathic pain was evaluated.

Methods: Mice were intraspinally injected with adenovirus for knockdown of USF2 (Ad-shUSF2) and then subjected to spinal nerve ligation (SNL) to induce neuropathic pain. Distribution and expression of USF2 were detected by western blot and immunofluorescence. Mechanical and thermal pain sensitivity were examined by paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL). Chromatin immunoprecipitation (ChIP) and luciferase activity assays were performed to detect binding ability between USF2 and SNHG5.

Results: The expression of USF2 was elevated and colocalized with astrocytes and microglia in L5 dorsal root ganglion (DRG) of SNL-induced mice. Injection of Ad-shUSF2 attenuated SNL-induced decrease of PWT and PWL in mice. Knockdown of USF2 increased the level of IL-10 but decreased TNF-α, IL-1β, and IL-6 in SNL-induced mice. Silence of USF2 enhanced protein expression of CD206 while reducing expression of CD16 and CD32 in SNL-induced mice. USF2 binds to promoter of SNHG5 and weakens SNL-induced up-regulation of SNHG5. SNHG5 binds to miR-181b-5p, and miR-181b-5p to interact with CXCL5.

Conclusion: Silence of USF2 ameliorated neuropathic pain, suppressed activation of M1 microglia, and inhibited inflammation in SNL-induced mice through regulation of SNHG5/miR-181b-5p/CXCL5 axis. Therefore, USF2/SNHG5/miR-181b-5p/CXCL5 might be a promising target for neuropathic pain. However, the effect of USF2/SNHG5/miR-181b-5p/CXCL5 on neuropathic pain should also be investigated in further research.

Background: The fetal brain undergoes a dynamic process of development during gestation, marked by well-orchestrated events such as neuronal proliferation, migration, axonal outgrowth, and dendritic arborization, mainly elucidated through histological studies. Ex vivo magnetic resonance imaging (MRI) has emerged as a useful tool for 3D visualization of the developing fetal brain, serving as a complementary tool to traditional histology.

Summary: In this review, we summarized the commonly employed ex vivo MRI techniques and their advances in fetal brain imaging, and proposed a standard protocol for postmortem fetal brain specimen collection and fixation. We then provided an overview of ex vivo MRI-based studies on the fetal brain.

Key messages: According to our review, ex vivo T1- or T2-weighted structural MRI has contributed to the characterization of the anatomy of transient neuronal proliferative zones, the basal ganglia, and the cortex. Diffusion MRI-related techniques, such as diffusion tensor imaging and tractography, have helped investigate the microstructural patterns of fetal brain tissue, as well as the early emergence and development of neuronal migration pathways and white matter bundles. Ex vivo MRI findings have shown strong histological correlations, supporting the potential of MRI in evaluating the developmental events in the fetal brain. Postmortem MRI examinations have also demonstrated comparable, and in certain cases, superior performance to traditional autopsy in revealing fetal brain abnormalities. In conclusion, ex vivo fetal brain MRI is an invaluable tool that provides unique insights into the early stages of brain development.

Introduction: The underlying neural and/or perceptual mechanisms of different visual illusions are still unknown; thus, they continue to be the focus of many ongoing studies. Inconsistencies persist in the empirical findings for understanding how the perception of these illusions evolves over the course of development.

Methods: We assessed 513 participants between 6.5 and 18.9 years of age, with 103 pairs of illusory and control images spanning five illusion types (Ebbinghaus, Müller-Lyer, Contrast, Moving Snake, and Subjective Contour). Misleading and helpful contexts were added when possible.

Results: In general, we found that, except for the Ebbinghaus illusion, susceptibility changes with age: while for the Müller-Lyer it decreases, for the Contrast, Moving Snake, and Kanizsa, susceptibility increases. Across all illusory conditions, participants' decision time decreased with age. Context also influenced the performance and choice latency. We also found a gender difference: boys were less susceptible than girls to Contrast and Moving Snake illusions and were faster to answer in Müller-Lyer illusion trials.

Conclusion: The current study found that susceptibility to illusions changes in a manner that is age-specific and, in some cases, sex-specific. The different developmental trajectories of the perception of visual illusions support the idea of the lack of a common neural and/or perceptual process behind them. We can suggest that at least some of the cognitive processes and neural pathways involved develop heterochronically.

Introduction: Pubertal maturation is marked by significant changes in stress-induced hormonal responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis, with prepubertal male and female rats often exhibiting greater HPA reactivity compared to adult males and females. Though the implications of these changes are unclear, elevated stress responsiveness might contribute to the stress-related vulnerabilities often associated with puberty.

Methods: The current experiments sought to determine whether differences in cellular activation, as measured by FOS immunohistochemistry, or excitatory ionotropic glutamate receptor subunit expression, as measured by qRT-PCR, in the paraventricular nucleus (PVN) were associated with these noted pubertal shifts in stress reactivity in male and female rats. As the PVN is the key nucleus responsible for activating the hormonal stress response, we predicted greater cellular activation and higher expression levels of glutamate receptor subunits in the PVN of prepubertal males and females compared to their adult counterparts.

Results: Our FOS data revealed that while prepubertal males showed greater stress-induced activation in the PVN than adult males, prepubertal females showed less activation than adult females. Moreover, many of the NMDA, AMPA, and kainate receptor subunits measured, including Grin1, Grin2b, Gria1, Gria2, Grik1, and Grik2, had higher expression levels in adults, particularly in males.

Conclusions: Though not supporting our initial predictions, these data do indicate that age and stress influence the activation of the PVN and the expression of glutamate receptor subunits important in its function. These data also suggest that the effects of age and stress are different in males and females. Though still far from a clear understanding of what mechanism(s) mediate pubertal shift in stress reactivity, these data add to our growing understanding of how age, stress, and sex influence HPA function.