Developmental Neuroscience最新文献

The aim of the study was to investigate three aspects of auditory function (auditory acuity, cochlear dysfunction, and auditory processing) in adolescents with fetal alcohol exposure without phenotypic changes. Fifty-one adolescents with and without intrauterine exposure to alcohol were selected from a cohort study. The summons, evaluation, and analysis of the results were carried out blindly regarding the respective exposure to alcohol. The auditory tests were pure-tone audiometry, transient otoacoustic emissions, and behavioral assessment of auditory processing (speech-in-noise, dichotic digits, and gap-in-noise). After testing, 45 adolescents were included in the evaluation and were divided into exposed (n = 22) and non-exposed (n = 23) groups. Hearing loss was identified in one subject in the exposed group (4.5%). In the absence of hearing loss, there were no significant differences in tonal thresholds or in the magnitudes of the sensory (cochlear) responses between groups (p > 0.05). There was also no difference between the two groups regarding performance on the processing tests (speech-in-noise p = 0.71, dichotic p = 0.94, and gap-in-noise p = 0.33). However, the exposed group had more cases of hearing disorders (hearing loss plus auditory processing disorders) than the non-exposed group (22.7% vs. 4.3%).

Alterations in the expression of genes encoding proteins involved in synapse formation, maturation, and function are a hallmark of many neurodevelopmental and psychiatric disorders. For example, there is reduced neocortical expression of the MET receptor tyrosine kinase (MET) transcript and protein in Autism Spectrum Disorder (ASD) and Rett syndrome. Preclinical in vivo and in vitro models manipulating MET signaling reveal that the receptor modulates excitatory synapse development and maturation in select forebrain circuits. The molecular adaptations underlying the altered synaptic development remain unknown. We performed a comparative mass spectrometry analysis of synaptosomes generated from the neocortex of wild type and Met null mice during the peak of synaptogenesis (postnatal day 14; data are available from ProteomeXchange with identifier PXD033204). The analyses revealed broad disruption of the developing synaptic proteome in the absence of MET, consistent with the localization of MET protein in pre- and postsynaptic compartments, including proteins associated with the neocortical synaptic MET interactome and those encoded by syndromic and ASD risk genes. In addition to an overrepresentation of altered proteins associated with the SNARE complex, multiple proteins in the ubiquitin-proteasome system and associated with the synaptic vesicle, as well as proteins that regulate actin filament organization and synaptic vesicle exocytosis/endocytosis, were disrupted. Taken together, the proteomic changes are consistent with structural and functional changes observed following alterations in MET signaling. We hypothesize that the molecular adaptations following Met deletion may reflect a general mechanism that produces circuit-specific molecular changes due to loss or reduction of synaptic signaling proteins.

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595, and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype "TTGGG" was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases, and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603 and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP, and female subgroups, indicating that Nogo-A might mainly affect mild types of CP and there might be sex-related differences.

Epidemiological studies show that social determinants of health are among the strongest factors associated with developmental outcomes after prenatal and perinatal brain injuries, even when controlling for the severity of the initial injury. Elevated socioeconomic status and a higher level of parental education correlate with improved neurologic function after premature birth. Conversely, children experiencing early life adversity have worse outcomes after developmental brain injuries. Animal models have provided vital insight into mechanisms perturbed by developmental brain injuries, which have indicated directions for novel therapeutics or interventions. Animal models have also been used to learn how social environments affect brain maturation through enriched environments and early adverse conditions. We recognize animal models cannot fully recapitulate human social circumstances. However, we posit that mechanistic studies combining models of developmental brain injuries and early life social environments will provide insight into pathways important for recovery. Some studies combining enriched environments with neonatal hypoxic injury models have shown improvements in developmental outcomes, but further studies are needed to understand the mechanisms underlying these improvements. By contrast, there have been more limited studies of the effects of adverse conditions on developmental brain injury extent and recovery. Uncovering the biological underpinnings for early life social experiences has translational relevance, enabling the development of novel strategies to improve outcomes through lifelong treatment. With the emergence of new technologies to analyze subtle molecular and behavioral phenotypes, here we discuss the opportunities for combining animal models of developmental brain injury with social construct models to deconvolute the complex interactions between injury, recovery, and social inequity.