Developmental Neuroscience最新文献

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.

Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.

Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.

Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.

Introduction: Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission that may be mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which can result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity and could influence the activity-dependent maturational process of these neurons.

Methods: In the present study, we used male and female Sprague Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (EA; 30-38 days old), late adolescence (LA; 40-48 days old), or young adulthood (60-68 days old). One day following exposure, effects of METH on PV cell and PNN expression were assessed using immunofluorescent labeling within the mPFC.

Results: METH exposure did not alter male PV neurons or PNNs. Females exposed in early adolescence or adulthood had more PV expressing neurons while those exposed in later adolescence had fewer, suggesting distinct windows of vulnerability to changes induced by METH exposure. In addition, females exposed to METH had more PNNs and more intense PV neuron staining, further suggesting that METH exposure in adolescence uniquely influences development of inhibitory circuits in the female mPFC.

Conclusions: This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.

Introduction Enhanced models for assessing cognitive function in the neonatal period are imperative in higher animals. Postnatal motor deficits, characteristic of cerebral palsy, emerge in newborn kits within our prenatal-rabbit model of hypoxia-ischemia (HI). In humans, prenatal HI leads to intellectual disability and cerebral palsy. In a study examining cognitive function in newborn rabbits, we explored several questions. Is there a distinction between conditioned and unconditioned kits? Can the kits discern the human face or the lab coat? Do motorically-normal kits, born after prenatal HI, exhibit cognitive deficits? Methods The conditioning protocol was randomly assigned to kits from each litter. For conditioning, the same human, wearing a lab coat, fed the rabbit kits for 9 days before the cognitive test. The 6-arm radial maze was chosen for its simplicity and ease of use. Normally appearing kits, born after uterine ischemia at 79% or 92% term in New Zealand White rabbits, were compared to Naïve kits. On postpartum day 22/23 or 29/30, the 6-arm maze helped determine if the kits recognized the original feeder from bystander (Test-1) or the lab coat on bystander (Test-2). The use of masks of feeder/bystander (Test-3) assessed confounding cues. A weighted score was devised to address variability in entry to maze arms, time, and repeated-trial learning. Results In conditioned kits, both Naïve and HI kits exhibited a significant preference for the face of the feeder, but not the lab coat. Cognitive deficits were minimal in normal-appearing HI kits. Conclusion The weighted score system was amenable to statistical manipulation.

Background: 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 was 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 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 reduced expression of CD16 and CD32 in SNL-induced mice. USF2 bind to promoter of SNHG5, and weakened SNL-induced up-regulation of SNHG5. SNHG5 bind 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.

Previous neuroimaging studies on arithmetic development have mainly focused on functional activation or functional connectivity between brain regions. It remains largely unknown how brain structures support arithmetic development. The present study investigated whether early gray matter structural covariance contributes to later gain in arithmetic ability in children. We used a public longitudinal sample comprising 63 typically developing children. The participants received structural magnetic resonance imaging scanning when they were 11 years old and were tested with a multiplication task at 11 years old (time 1) and 13 years old (time 2), respectively. Mean gray matter volumes were extracted from eight brain regions of interest to anchor salience network (SN), frontal-parietal network (FPN), motor network (MN), and default mode network (DMN) at time 1. We found that longitudinal gain in arithmetic ability was associated with stronger structural covariance of the SN seed with frontal and parietal regions and stronger structural covariance of the FPN seed with insula, but weaker structural covariance of the FPN seed with motor and temporal regions, weaker structural covariance of the MN seed with frontal and motor regions, and weaker structural covariance of the DMN seed with temporal region. However, we did not detect correlation between longitudinal gain in arithmetic ability and behavioral measure or regional gray matter volume at time 1. Our study provides novel evidence for a specific contribution of gray matter structural covariance to longitudinal gain in arithmetic ability in childhood.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises four molecularly and clinically distinct subgroups (termed WNT, SHH, group 3, and group 4). Prognosis varies based on genetic and pathological features associated with each molecular subgroup. WNT-MB, considered low-risk, is rarely metastatic and contains activating mutations in CTNNB1; group 3-MB (GRP3-MB), commonly classified as high-risk, is frequently metastatic and can contain genomic alterations, resulting in elevated MYC expression. Here, we compare model systems of low-risk WNT-MB and high-risk GRP3-MB to identify tumor and microenvironment interactions that could contribute to features associated with prognosis. Compared to GRP3-MB, we find that WNT-MB is enriched in gene sets related to extracellular matrix (ECM) regulation and cellular adhesion. Exogenous expression of MycT58A in a murine WNT-MB model significantly accelerates growth and results in metastatic disease. In addition to decreased ECM regulation and cell adhesion pathways, we also identified immune system interactions among the top downregulated signaling pathways following MycT58A expression. Taken together, our data provide evidence that increased Myc signaling can promote the growth and metastasis in a murine model of WNT-MB.

Introduction: C-terminal-binding protein 1 (CtBP1) is a multi-functional protein with well-established roles as a transcriptional co-repressor in the nucleus and a regulator of membrane fission in the cytoplasm. Although CtBP1 gene abnormalities have been reported to cause neurodevelopmental disorders, the physiological role and expression profile of CtBP1 remains to be elucidated.

Methods: In this study, we used biochemical, immunohistochemical, and immunofluorescence methods to analyze the expression of CtBP1 during mouse brain development.

Results: Western blotting analyses revealed that CtBP1 appeared to be expressed mainly in the central nervous system throughout the developmental process. In immunohistochemical analyses, region-specific nuclear as well as weak cytoplasmic distribution of CtBP1 was observed in telencephalon at embryonic day (E)15 and E17. It is of note that CtBP1 was barely detected in axons but observed in the nucleus of oligodendrocytes in the white matter at E17. As to the cerebellum at postnatal day 30, CtBP1 appeared to be expressed in the nucleus and cytoplasm of Purkinje cells, the nucleus of granule cells and cells in the molecular layer (ML), and the ML per se, where granule cell axons and Purkinje cell dendrites are enriched. In addition, CtBP1 was detected in the cerebellar nuclei.

Conclusion: The obtained results suggest involvement of CtBP1 in brain function.

Background: Ependymomas are the third most common brain cancer in children and have no targeted therapies. They are divided into at least 9 major subtypes based on molecular characteristics and major drivers and have few genetic mutations compared to the adult form of this disease, leading to investigation of other mechanisms.

Summary: Epigenetic alterations such as transcriptional programs activated by oncofusion proteins and alterations in histone modifications play an important role in development of this disease. Evidence suggests these alterations interact with the developmental epigenetic programs in the cell of origin to initiate neoplastic transformation and later disease progression, perhaps by keeping a portion of tumor cells in a developmental, proliferative state.

Key messages: To better understand this disease, research on its developmental origins and associated epigenetic states needs to be further pursued. This could lead to better treatments, which are currently lacking due to the difficult-to-drug nature of known drivers such as fusion proteins. Epigenetic and developmental states characteristic of these tumors may not just be potential therapeutic targets but used as a tool to find new avenues of treatment.

Despite advances in perinatal medicine, racial disparity in birth outcomes remains a public health problem in the USA. The underlying mechanisms for this long-standing racial disparity are incompletely understood. This review presents transgenerational risk factors for racial disparities in preterm birth, exploring the impact of interpersonal and structural racism, theoretical models of stress, and biological markers of racial disparities.