Developmental Neuroscience最新文献

Background: Healthcare costs are rising at an exponential rate. Given the constraints of limited resources, it is essential to make informed decisions about priorities to ensure the best possible health outcomes globally. The history of medicine illustrates how these priorities have shifted over time - from early focus on infectious diseases to later emphasis on noncommunicable conditions such as metabolic disorders. Today, neurodegenerative diseases and aging brain are the forefront of medical research, as these conditions profoundly affect individuals, families, and society.

Summary: One in three people will experience a mental health disorder in their lifetime, yet it is not widely recognized that many of these conditions may have origins in pre-birth experiences and early life influences. Disruptions in progenitor proliferation, neuronal and glial migration, and differentiation during prenatal development can contribute to lifelong neurodevelopmental abnormalities. Despite the fundamental importance of brain development, most of the neuroscience funding is allocated to studying neurodegeneration, such as dementia and Parkinson's disease, while early life influences remain underexplored. Crucially, the impact of developmental factors begins even before conception. Environmental risks extend beyond direct maternal exposures during pregnancy; they include cumulative parental exposure to teratogenic agents affecting both male and female gametes, as well as early life environmental exposures affecting newborns, infants, and children. These influences are complex yet highly relevant to long-term health outcomes.

Key messages: We urge greater recognition of the developmental origins of disease and advocate for increased investment in preventive strategies. These include lifestyle modifications, dietary improvements, targeted supplementation, regular exercise, and minimizing exposure to environmental pollutants. Addressing these factors proactively could yield profound benefits for both individual and public health.

Introduction: Gyrification is a shared phenotype of brain development across many species. The identification of human- and primate-specific genes is a topic of great research interest to uncover the genetic mechanisms that drive human gyrification. Here we investigated a human transcript variant of FOXM1 with a unique ninth exon proposed to have a crucial role in primate gyrification.

Method: We performed comprehensive bioinformatic analyses, including several BLASTs and multiple sequence alignment, utilising available deposited sequencing data. We aimed to determine the degree of conservation of human FOXM1 exon 9 across a wide range of species, with a particular focus on gyrencephalic primates. Furthermore, we aimed to determine the degree of conservation of the remaining regions of FOXM1 across a subset of gyrencephalic and lissencephalic species.

Results: Our results revealed that the exon is only partially detected in four other primates, challenging its presumed conservation in humans, apes, and other primates. The remaining regions of FOXM1 had a remarkably high level of conservation, and, given its role in regulating proliferation and differentiation, the results suggested that FOXM1 may be required for early brain development across all species. However, the sporadic presence of the exon 9 sequence even in other gyrencephalic primates raises questions about its indispensability in the process of gyrification.

Conclusion: Therefore, we conclude that the FOXM1 transcript variant comprising the exon 9 sequence in its entirety could be more appropriately reclassified as a human-specific cortical folding variant not found in other species. This research lays the foundation for further investigating the role of FOXM1 exon 9 in human gyrification and brain development.

Introduction: Hypoxia-inducible factor-1α (HIF-1α) has a wide-ranging role in the cellular responses to hypoxia. We previously found that neuron-specific HIF-1α-deficient mice (HIF-KO) that underwent neonatal hypoxia-ischemia (HI) had increased brain injury suggesting its neuroprotective function. To investigate whether HIF-1α is also involved in the mechanisms of protection by hypothermia (HT), the standard of care for hypoxic-ischemic encephalopathy, we tested the effect of HT on HIF-KO and wild-type (WT) littermates after HI in postnatal day 9 mice.

Methods: Cooling at 32°C began 1 h following HI and lasted for 3.5 h. Mice were perfused 5-7 days later for histological determination of injury severity. For Western blots, mice were killed 4 h or 24 h after HI with HT or HI with normothermia (NT) and ipsilateral cortices and hippocampi were evaluated for expression of HIF-1α, spectrin, ERK1/2, phosphorylated-ERK1/2 (p-ERK), and RNA-binding motif protein 3 (RBM3), one of the main cold-inducible mRNA-binding proteins.

Results: Histological evaluation showed WT mice with HT had less injury than WT with NT, but HIF-KO mice showed no reduction of injury with HT. Regionally, the reduction of injury in WT with HT is greater in the hippocampus than in the cortex. Protein expression of HIF-1α was lower in HIF-KO cortex at 4 h with NT or HT and at 24 h with NT, but HIF-1α was higher in WT with NT at 24 h. Expression of spectrin 145/150 in WT cortex with HT was not different than sham at 4 h, indicating limitation of necrosis with HT. In the HIF-KO cortex at 4 h spectrin 145/150 was higher in both NT and HT, indicating no protection with HT. In the hippocampus at 4 h and 24 h, spectrin 145/150 was elevated in all groups compared to sham. ERK activity, as represented by the ratio of p-ERK/ERK, was upregulated at 24 h in the cortex in WT with NT or HT compared to sham and in HIF-KO mice with NT or HT treatment compared to sham. RBM3 was elevated at 4 h in both WT and HIF-KO cortex with HT, but there was no change in the hippocampus.

Conclusion: These results support a critical role for HIF-1α in the mechanisms of protection with HT.

Background: Homeostasis of water content in the brain during fetal development is of crucial physiological importance. Aquaporins (AQPs) play a critical role in maintaining brain water balance, supporting normal brain development, and are increasingly recognized for their relevance in understanding neurodevelopmental disorders.

Summary: This review provides a comprehensive overview of AQPs and their essential roles in the central nervous system (CNS), specifically AQP4, AQP11, and AQP9, which play a crucial role in water transport in the brain, maintaining water homeostasis and facilitating water movement across cell membranes. The review also highlights how disruptions in AQP expression and function may contribute to the pathology of neurodevelopmental disorders such as autism and Fragile X syndrome.

Key messages: AQPs are vital for brain water regulation and normal neural development. Altered expression or function of AQPs can impact blood-brain barrier integrity, neuroinflammation, and synaptic activity. AQP dysfunctions are linked to neurodevelopmental disorders and may represent promising therapeutic targets.

Introduction: Unilateral brain injury in neonates results in largely contralateral hand function impairment in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To test this, we first developed a model of sensory tract injury in neonatal rats by targeting the thalamocortical tract (TCT), and then we used this model to assess the effects of sensory lesions on paw use.

Methods: In the postnatal day 7 rats, we used three types of lesions to the TCT: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. To test the forelimb use, the cylinder exploration and pasta handling tests were used.

Results: Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the TCT while sparing the adjacent corticospinal tract in the internal capsule. Given that electrolytic lesions were the most specific and sensitive for targeting the TCT, this model was used for behavioral experiments to measure the impact of sensory tract lesion on dexterity. Lesions to the TCT were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury.

Conclusion: Overall, specific sensory system lesions of the TCT impair forelimb use, suggesting a key role for skilled movement.

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.