Developmental Neurobiology最新文献

This study reviews the roles of proton electrochemical gradients in ubiquitous mitochondrial energy production systems in cellular activation and functions in neurosensory signaling. Proton electrochemical gradients crucially shaped the evolution of life. The emergence of the proton-motive force in mitochondria was fundamental in energy production and central to the function of eukaryotic cells. Dysfunctional mitochondria, however, result in impaired formation of proton gradients and a wide spectrum of diseases. This is particularly prominent in tissues with high energetic demands, such as muscle and nervous tissues. Oxidant stress generated by dysfunctional proton conductance in the brain results in Alzheimer's and Parkinson's disease, muscular sclerosis, amyotrophic sclerosis, and Huntington's disease. In these disorders, oxidative stress, protein misfolding, and neuroinflammation lead to dysfunctional neuronal activity, neuronal damage, and death. Advancements in nanozyme-engineered synthetic enzymes offer a promising innovative approach to the treatment of these disorders. Nanozymes target proton conductance and the oxidant species they generate, scavenging oxygen free radicals and restoring redox balance, and offer neuronal protection and functional recovery of brain tissues. Neural injury and associated neurological diseases affect almost 1 billion people globally, so there is a clear need to develop effective methods that stimulate neural repair and regeneration. Glycosaminoglycans with proton capture and transport properties regulate intercellular signaling processes, synaptic functions, and cellular communication. Electroconductive hydrogels are showing impressive results in neural repair and regeneration. Glycosaminoglycans, particularly keratan sulfate, show useful electroconductive proton capture and transport properties, suggesting they may be worth evaluation in such procedures.

Ischemic stroke is a prominent cause of morbidity and mortality, affecting numerous people worldwide. The exact role of Maixuekang capsule in cerebral ischemia/reperfusion injury (CI/RI) remains elusive. The present study aimed to delve into the neuroprotective potential of Maixuekang in CI/RI rats. Utilizing the HREB database, leech ingredients were retrieved, while GeneCards, therapeutic target database (TTD), and DisGeNET databases were used to predict cerebral infarction targets. Search tool for the retrieval of interacting genes/proteins (STRING) database was adopted to identify overlapping genes, and Cytoscape 3.9.1 to analyze core targets. The gene ontology (GO)/ Kyoto encyclopedia of genes and genomes (KEGG) pathway were analyzed and neurological function was assessed via Longa scoring. The 2,3,5-triphenyltetrazolium chloride (TTC), Golgi, hematoxylin and eosin (H&E), and Nissl stains were adopted to observe cerebral infarction and pathological changes. The neuronal apoptosis, hypoxia inducible factor 1 alpha (HIF1A), myeloperoxidase (MPO) and inflammatory factors in rat were measured. Results suggested Maixuekang reduced the neurological function score and the cerebral infarction incidence in CI/RI rats. After taking Maixuekang, the number of dendritic spines of CI/RI rats increased, the neuronal damage degree in the ischemic cortical area reduced, and the neurons morphology improved. In addition, Maixuekang reduced the blood–brain barrier (BBB) damage and brain tissue water content by decreasing neuronal apoptosis rate, Bax expression, neutrophil infiltration, inflammatory factor levels, and increasing Bcl2 by decreasing HIF1A in CI/RI rat tissues. Collectively, Maixuekang could reduce neurological function, cerebral infarction rate, blood–brain barrier damage, neuroinflammation and downregulates HIF1A in tissues of CI/RI rats.

The expression patterns of key membrane pumps and ion channels involved in endolymph cycling have been studied in the rodent inner ear and the developing and adult human cochlea. However, little is known about their expression during the development of the human vestibular system. In this study, we provide a comprehensive overview of expression profiles of ion pumps, cotransporters, and exchangers in the developing human utricle and ampullae from fetal week (FW) 8 to 17. Immunohistochemistry analysis revealed that ATP1A1 and ATP1B2 co-localize at the basolateral membranes of dark cells. In addition, BSND expression was observed in transitional cells and dark cells in both the ampulla and utricle from FW10. We further characterized the expression of gap junction proteins (GJA1, GJB2, and GJB6) and found that KCNQ1 was expressed by transitional cells and dark cells starting from FW14. SLC12A2 immunostaining was detected in dark cells around FW10. Lastly, we investigated the spatiotemporal expression of pendrin. These detailed observations of protein expression during human inner ear development enhance our understanding of endolymph homeostasis.

Neural stem cells (NSCs) play a crucial role in neural regeneration following spinal cord injury (SCI) owing to their self-proliferative and multidirectional differentiation capabilities. This study examined the biological properties of adult spinal cord-derived NSCs (sp-NSCs) and the role of Notch receptors in regulating their activation. NSCs were isolated from the spinal cords of 8-week-old C57/BL6 mice, and their biological properties, including the gene expression profile of Notch receptors, were subsequently analyzed using single-cell RNA sequencing (scRNA-Seq) and bioinformatics. The NSCs were subsequently infected with lentiviral vectors encoding Notch1 shRNA, Notch2 shRNA, and a combination of Notch1 and Notch2 shRNA sequences, and evaluated using Sphere assays and EdU staining to determine their activation effects. The expression levels of downstream genes, NICD and Rbpj, in the Notch signaling pathway, as well as the related target genes, Hes1 and Hey1, were subsequently quantified using Western blot analysis. Intact adult mouse sp-NSCs predominantly existed in a quiescent state, with their population increasing significantly with age. Notch receptors served as critical regulators of adult sp-NSC activation. Notably, Notch1 expression was significantly elevated compared to Notch2 and Notch3, demonstrating its predominant role in sustaining NSC activation. In contrast, Notch2 and Notch3 were primarily responsible for maintaining NSCs in a quiescent state. Overall, both Notch1 and Notch2 signals are involved in different regulatory roles that facilitate the activation and fate determination of NSCs via NICD-Rbpj.

The retinotectal projection in Xenopus laevis is topographically organized. During the early development of the Xenopus visual system, the optic tectum increases considerably in volume, and retinotectal axons and dendrites undergo extensive activity-dependent remodeling. We have previously observed marked changes in the three-dimensional layout of the tectal retinotopic functional map over the course of a few days. This raised the question of whether such functional reorganization might be attributable to the migration and structural remodeling of tectal neurons as the brain grows. To examine changes in map topography in the context of individual tectal neuron morphology and location, we performed calcium imaging in the optic tecta of GCaMP6s-expressing tadpoles in parallel with structural imaging of tectal cells that were sparsely labeled with Alexa 594-dextran dye. We performed functional and structural imaging of the optic tectum at two developmental time points, recording the morphology of the dextran-labeled cells and quantifying the changes in their positions and the spanning volume of their dendritic fields. Comparing anatomical growth to changes in the functional retinotopic map at these early stages, we found that dendritic arbor growth kept pace with the overall growth of the optic tectum and that individual neurons continued to receive widespread visual field input, even as the tectal retinotopic map evolved markedly over time. This suggests a period of initial growth during which inputs to individual tectal neurons maintain diffuse connectivity and broad topographic integration.