Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 5 480
Страница 298 из 548-
An association of subtotal cerebellar agenesis with organoid nevus--a possible new variety of neurocutaneous syndrome.
A quite unique patient aged 13, characterized by a combination of organoid nevus on the left scalp and subtotal cerebellar agenesis accompanied by hypoplasia of the pons and midbrain, was reported. Cardinal clinical features consisted of nonprogressive cerebellar manifestations including intention tremor and ataxia, speech and visual disturbance and mental retardation. An electronystagmogram demonstrated periodic alternating nystagmus. A clinical diagnosis of cerebellar agenesis in this case was made through the demonstration of characteristic features in metrizamide CT and midline sagittal tomography of metrizamide cisternography of the posterior fossa. An extensive review of the literature revealed three papers dealing with organoid nevus associated with various neurological abnormalities, but no single case with a similar combination of cutaneous organoid nevus and cerebellar agenesis had been reported.
-
Identification of neural oscillations and epileptiform changes in human brain organoids.
Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.
-
Fetal exposure to valproic acid dysregulates the expression of autism-linked genes in the developing cerebellum.
Autism spectrum disorder (ASD) includes a set of highly heritable neurodevelopmental syndromes characterized by social and communication impairment, repetitive behaviour, and intellectual disability. Although mutations in multiple genes have been associated to ASD, most patients lack detectable genetic alterations. For this reason, environmental factors are commonly thought to also contribute to ASD aetiology. Transcriptome analyses have revealed that autistic brains possess distinct gene expression signatures, whose elucidation can provide insights about the mechanisms underlying the effects of ASD-causing genetic and environmental factors. Herein, we have identified a coordinated and temporally regulated programme of gene expression in the post-natal development of cerebellum, a brain area whose defects are strongly associated with ASD. Notably, this cerebellar developmental programme is significantly enriched in ASD-linked genes. Clustering analyses highlighted six different patterns of gene expression modulated during cerebellar development, with most of them being enriched in functional processes that are frequently dysregulated in ASD. By using the valproic acid mouse model of ASD, we found that ASD-linked genes are dysregulated in the developing cerebellum of ASD-like mice, a defect that correlates with impaired social behaviour and altered cerebellar cortical morphology. Moreover, changes in transcript levels were reflected in aberrant protein expression, indicating the functional relevance of these alterations. Thus, our work uncovers a complex ASD-related transcriptional programme regulated during cerebellar development and highlight genes whose expression is dysregulated in this brain area of an ASD mouse model.
-
Is a conscious silicon brain achievable?
The biological mind is created by brain activity, and the mind's experiences and thoughts can change its structure and function. To construct a digital twin brain, it is possible to decode the unique activity of the human brain for each of the mental faculties responsible for all mental phenomena, create their digital twins, and connect them to the reconstructed and simulated neural circuits of human brain. Another strategy is to reconstruct and simulate the neural circuits of functional human brain organoids individually and in assembloids to match the functional characteristics of neural circuits through iterative simulations and experiments, and combine them with artificial intelligence (AI) to create a kind of silicon brain. Then, with the convergence of silicon brain technologies, AI avatars, the source of embodied sense data, and metaverse, the source of environmental sense data, a complex system can be created that may represent a level of consciousness. The first approach faces major issues in data acquisition, computational requirements, and the integration of diverse data sources. The second approach is a practical solution that can be achieved very quickly and can be really effective in addressing the challenges of the first approach. Building a silicon brain will increase our understanding of the mechanisms behind mind and the functioning of consciousness. This will improve brain models and will have many applications, mainly useful for achieving better progress in medical science.
-
Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids.
Studying the non-human primate (NHP) brain is required for the translation of rodent research to humans, but remains a challenge for molecular, cellular, and circuit-level analyses in the NHP brain due to the lack of in vitro NHP brain system. Here, we report an in vitro NHP cerebral model using marmoset (Callithrix jacchus) embryonic stem cell-derived cerebral assembloids (CAs) that recapitulate inhibitory neuron migration and cortical network activity. Cortical organoids (COs) and ganglionic eminence organoids (GEOs) were induced from cjESCs and fused to generate CAs. GEO cells expressing the inhibitory neuron marker LHX6 migrated toward the cortical side of CAs. COs developed their spontaneous neural activity from a synchronized pattern to an unsynchronized pattern as COs matured. CAs containing excitatory and inhibitory neurons showed mature neural activity with an unsynchronized pattern. The CAs represent a powerful in vitro model for studying excitatory and inhibitory neuron interactions, cortical dynamics, and their dysfunction. The marmoset assembloid system will provide an in vitro platform for the NHP neurobiology and facilitate translation into humans in neuroscience research, regenerative medicine, and drug discovery.
-
Brain corticogenesis promotes SARS-CoV-2 neuro-glial tropism through lipid-dependent viral replication.
While extensive research has examined the neuroinvasiveness of SARS-CoV-2, its relationship with brain maturation remains unclear. Using a multi-omics approach, we established cerebral organoid (CBO) at day 60 (EB60) and day 120 (EB120) to model immature and mature developmental stages. We found that enhanced corticogenesis and gliogenesis during maturation are associated with substantial alterations in lipid metabolism, functionally linking these processes to coordinated molecular and functional brain development. Leveraging this model, we provide the first quantitative insights into long-term viral propagation kinetics up to 20 days post-infection, revealing significantly higher infectivity in mature CBOs. Single-cell transcriptomics, RT-qPCR, and immunohistochemistry revealed the upregulation of lipid-associated genes in EB120, suggesting a key driver of increased susceptibility. Consistently, pharmacological lipid reduction attenuated SARS-CoV-2 infection. Our findings establish a mechanistic link between intrinsic brain maturation and viral susceptibility mediated by lipid remodeling, suggesting lipid-lowering strategies as potential candidates for therapeutic repurposing in COVID-19.
-
Brain organoids fill the gap.
-
Molecular mechanisms of silver nanoparticle-induced neurotoxic injury and new perspectives for its neurotoxicity studies: A critical review.
Silver nanoparticles (AgNPs) garnered significant attention and applications in the field of nanotechnology due to their unique physicochemical properties. However, with the increasing exposure of AgNPs in the environment and biological systems, concerns about their potential neurotoxicity have also risen. Recent studies on the neurotoxic effects and mechanisms of AgNPs have often relied on traditional toxicological research methods and perspectives. This reliance has limited the extrapolation of these findings to the human brain environment and hindered a deep understanding of the neurotoxicity of AgNPs. This review first outlines the molecular mechanisms of AgNPs-induced neurotoxic injury from a traditional research perspective, identifying oxidative stress, inflammatory responses, and autophagy disorders as key areas of current research. Related molecular signaling pathways, including the nuclear transcription factor-κB (NF-κB) signaling pathway, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and the calcium signaling pathway, have been implicated in the neurotoxic injury process induced by AgNPs. Subsequently, we elucidated the unique advantages of the 3D brain organoids applied to the neurotoxicity study of AgNPs by drawing on relevant studies in the same field. We also emphasize that establishing a standardized 3D brain organoids construction platform is a crucial prerequisite for its widespread application. Furthermore, we suggest that future studies should explore the neurotoxicity mechanisms of AgNPs through the lenses of "adaptive homeostasis" and "structure-activity relationship analysis". In conclusion, the neurotoxicity of AgNPs should be comprehensively evaluated by integrating new research techniques and perspectives, ultimately allowing these nanoparticles to better serve human society.
-
Junctional instability in neuroepithelium and network hyperexcitability in a focal cortical dysplasia human model.
Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options. Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids. Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.
-
Chromatin dynamics in human brain development and disease.
Chromatin-related genes are frequently mutated in neurodevelopmental disorders; yet, the mechanisms by which these perturbations disrupt brain assembly and function are not understood. Here, we describe how recent advances in transcriptional and chromatin profiling in combination with cellular models are beginning to inform our understanding of neurodevelopment and chromatinopathies.