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 302 из 548-
Effects of microplastics and nanoplastics on the brain and behavior: Evidence from rodent and human studies.
Microplastics (MPs) and nanoplastics (NPs) pose serious environmental and health risks and have made plastic pollution a major concern worldwide. They have been detected in terrestrial and aquatic species, including humans, and have been linked to increased risks of cardiovascular, respiratory and metabolic diseases. However, a critical question remains regarding whether plastic pollution also affects brain function and behavior. This review summarizes the current state of knowledge on the neurotoxic effects of MPs and NPs (MNPs) in the brain and their impact on behavior in both humans and rodents. We analyzed recent studies across multiple experimental approaches, including in vitro assays, animal models, human biomonitoring, and emerging technologies (i.e., brain organoids) to provide a comprehensive overview of MNP-induced effects. Findings are organized and discussed in terms of their influence on behavior, brain neurotransmission and function, and mechanistic pathways underlying neurotoxicity. We conclude that clarifying how MNPs affect neural systems and behavior, and exploring strategies to prevent or reverse their neurotoxic effects, will be crucial for safeguarding brain health in an increasingly plastic-contaminated world.
-
Emerging Methods in Modeling Brain Development and Disease with Human Pluripotent Stem Cells.
The Nobel Prize-winning discovery that human somatic cells can be readily reprogrammed into pluripotent cells has revolutionized our potential to understand the human brain. The rapid technological progression of this field has made it possible to easily obtain human neural cells and even intact tissues, offering invaluable resources to model human brain development. In this chapter, we present a brief history of hPSC-based approaches to study brain development and then, provide new insights into neurological diseases, focusing on those driven by aberrant cell death. Furthermore, we will shed light on the latest technologies and highlight the methods that researchers can use to employ established hPSC approaches in their research. Our intention is to demonstrate that hPSC-based modeling is a technical approach accessible to all researchers who seek a deeper understanding of the human brain.
-
COVID-19 - prime time for microphysiological systems, as illustrated for the brain.
The development of therapies for and preventions against infectious diseases depends on the availability of disease models. Bioengineering of human organoids and organs-on-chips is one extremely promising avenue of research. These miniature, laboratory-grown organ systems have been broadly used during the ongoing, unprecedented coronavirus 2019 (COVID-19) pandemic to show the many effects of the etiologic agent, severe acute respiratory coronavirus 2 (SARS-CoV-2) on human organs. In contrast, exposure of most animals either did not result in infection or caused mild clinical signs - not the severe course of the infection suffered by many humans. This article illuminates the opportunities of microphysiological systems (MPS) to study COVID-19 in vitro, with a focus on brain cell infection and its translational rel-evance to COVID-19 effects on the human brain. Neurovirulence of SARS-CoV-2 has been reproduced in different types of human brain organoids by 10 groups, consistently showing infection of a small portion of brain cells accompanied by limited viral replication. This mirrors increasingly recognized neurological manifestations in COVID-19 patients (evidence of virus infection and brain-specific antibody formation in brain tissue and cerebrospinal fluid). The pathogenesis of neuro-logical signs, their long-term consequences, and possible interventions remain unclear, but future MPS technologies offer prospects to address these open questions.
-
Hominoid-specific retrotransposons fuel regulatory novelty in early brain development.
Transposable elements can drive genetic innovation. In this issue of Cell Genomics, Adami et al.1 investigate the impact of hominoid-specific L1 retrotransposons on early embryonic and brain development. Using induced pluripotent stem cells and cerebral organoid models, multi-omics, and CRISPRi-mediated silencing, they uncover a cis-regulatory role for these young retrotransposons in early human brain development.
-
Bemnifosbuvir and remdesivir inhibit tick-borne encephalitis virus infection in complementary in vitro and ex vivo disease models.
The geographical distribution and incidence of tick-borne encephalitis (TBE) have steeply increased over the past decades, raising to represent a major health concern in Asia and Europe. Symptoms of TBE, caused by infections with tick-borne encephalitis virus (TBEV), range from mild flu-like symptoms to severe neurological disease, often accompanied by long-term sequelae persisting for several years following pathogen encounter. While effective vaccines against TBEV are available, no antiviral drugs are currently approved and therapeutic options for patients suffering from TBE are limited to supportive measures. Compounds able to disrupt viral nucleic acid synthesis bear the potential of effectively limiting viral replication and spread. Seeking to fill the therapeutic gap, we evaluated the efficacy of a panel of approved and investigational antiviral compounds in containing TBEV infection. Combining several cell lines, human neural organoids, and organotypic rat brain slice cultures, we found that the nucleotide analogs remdesivir and bemnifosbuvir efficiently limit viral replication. Through infectious virus quantification, immunofluorescence analysis, and flow cytometry, we report significant, dose-dependent reduction of viral loads across all models used with inhibition observed at low doses for both drugs. Notably, while we observed bemnifosbuvir to be well tolerated, we report important cytotoxicity of remdesivir when applied to human neural organoids. Our findings identify bemnifosbuvir and remdesivir as novel treatment strategies for TBE, providing an accessible and timely response to a clinical challenge of pressing concern.
-
Nanocage encapsulation improves antiepileptic efficiency of phenytoin.
More than 30% of patients with epilepsy progress to drug-resistant epilepsy, leading to a significant increase in morbidity and mortality of epilepsy. The limitation of epileptic drug to reach the epileptogenic focus is the critical reason, and the blood-brain barrier (BBB) plays a crucial role. Here, we successfully constructed a hepatitis B core (HBc) protein nanocage (NC) with the insertion of brain target TGN peptide for facilitating epileptic drug phenytoin delivery to the brain. Our results demonstrated that this nanocage can specifically and efficiently target the brain tissue by 2.4 fold and increase the antiepileptic efficiency of phenytoin about 100 fold in pilocarpine induced models of epilepsy. Both in vivo mice and in vitro human neural three-dimensional cortical organoids demonstrated high penetration ability. These functions are achieved through the facilitation of brain target peptide TGN rather than disruption of brain blood barrier. In summary, we presented an efficient antiepileptic drug delivery nanocage for the treatment of refractory epilepsy. Moreover, this therapeutic modulation also provides promising strategy for other intractable neurological disease.
-
Human Cortical Neuron Generation Using Cell Reprogramming: A Review of Recent Advances.
The study and treatment of neurological disorders have been hampered by a lack of access to live, healthy, or disease-affected human neurons. The recent advances in the field of cell reprogramming offer exciting new possibilities for disease modeling, drug development, and cell-based therapies. Since the derivation of human embryonic stem cells (hESCs) and their differentiation into neurons, cell reprogramming technologies have built on these protocols to generate mature human neurons of disease-associated phenotypes from somatic cells. Mechanistic knowledge of neural patterning and neurogenesis has been essential for the establishment of reprogramming strategies that employ a combination of transcription factors and small molecules selected due to their critical role in brain development. The generation of reprogrammed human neurons has the potential to further enhance our knowledge of pathways underlying the developmental process of the human brain, the current knowledge of which has predominantly come from animal studies, postmortem tissue, and most recently hESCs. Somatic cell reprogramming began in 2006 with the first report of induced pluripotent stem cell (iPSC) derivation from mouse fibroblasts. This has now expanded to direct-to-induced neuron and direct-to-induced neural stem or precursor reprogramming using a variety of viral and nonviral delivery methods. Most recently, iPSC technology has been extended to the development of three-dimensional brain structures referred to as brain spheroids or organoids. This review will discuss the reprogramming strategies that have been formulated to generate cortical neurons that are associated with many diseases, including autism spectrum disorders and schizophrenia.
-
Ethics and regulation of neuronal optogenetics in the European Union.
Neuronal optogenetics is a technique to control the activity of neurons with light. This is achieved by artificial expression of light-sensitive ion channels in the target cells. By optogenetic methods, cells that are naturally light-insensitive can be made photosensitive and addressable by illumination and precisely controllable in time and space. So far, optogenetics has primarily been a basic research tool to better understand the brain. However, initial studies are already investigating the possibility of using optogenetics in humans for future therapeutic approaches for neuronal based diseases such as Parkinson's disease, epilepsy, or to promote stroke recovery. In addition, optogenetic methods have already been successfully applied to a human in an experimental setting. Neuronal optogenetics also raises ethical and legal issues, e.g., in relation to, animal experiments, and its application in humans. Additional ethical and legal questions may arise when optogenetic methods are investigated on cerebral organoids. Thus, for the successful translation of optogenetics from basic research to medical practice, the ethical and legal questions of this technology must also be answered, because open ethical and legal questions can hamper the translation. The paper provides an overview of the ethical and legal issues raised by neuronal optogenetics. In addition, considering the technical prerequisites for translation, the paper shows consistent approaches to address these open questions. The paper also aims to support the interdisciplinary dialogue between scientists and physicians on the one hand, and ethicists and lawyers on the other, to enable an interdisciplinary coordinated realization of neuronal optogenetics.
-
Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data.
Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk tissue RNA sequencing (RNA-seq), single-cell/nuclei (sc/sn) RNA-seq, and immunohistochemistry. A total of 1,130,767 nuclei per cells from 149 adult postmortem brains and 72 organoid samples were used. The results showed the best performance of dtangle for estimating cell proportions and bMIND for estimating sample-wise cell-type gene expressions. For eight brain cell types, 25,273 cell-type eQTLs were identified with deconvoluted expressions (decon-eQTLs). The results showed that decon-eQTLs explained more schizophrenia GWAS heritability than bulk tissue or single-cell eQTLs did alone. Differential gene expressions associated with Alzheimer's disease, schizophrenia, and brain development were also examined using the deconvoluted data. Our findings, which were replicated in bulk tissue and single-cell data, provided insights into the biological applications of deconvoluted data in multiple brain disorders.
-
Cellular mechanisms underlying neurological/neuropsychiatric manifestations of COVID-19.
Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection manifest mainly respiratory symptoms. However, clinical observations frequently identified neurological symptoms and neuropsychiatric disorders related to COVID-19 (Neuro-SARS2). Accumulated robust evidence indicates that Neuro-SARS2 may play an important role in aggravating the disease severity and mortality. Understanding the neuropathogenesis and cellular mechanisms underlying Neuro-SARS2 is crucial for both basic research and clinical practice to establish effective strategies for early detection/diagnosis, prevention, and treatment. In this review, we comprehensively examine current evidence of SARS-CoV-2 infection in various neural cells including neurons, microglia/macrophages, astrocytes, pericytes/endothelial cells, ependymocytes/choroid epithelial cells, and neural stem/progenitor cells. Although significant progress has been made in studying Neuro-SARS2, much remains to be learned about the neuroinvasive routes (transneuronal and hematogenous) of the virus and the cellular/molecular mechanisms underlying the development/progression of this disease. Future and ongoing studies require the establishment of more clinically relevant and suitable neural cell models using human induced pluripotent stem cells, brain organoids, and postmortem specimens.