Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 5 480
Page 304 of 548-
Gut-brain axis in Alzheimer's disease: neural and immune circuits linking peripheral dysbiosis to neurodegeneration.
Alzheimer's disease (AD) is increasingly conceptualized as a system-level disorder shaped by bidirectional communication between the gut and the brain. The gut-brain axis (GBA) integrates neural, immune, and metabolic signaling pathways that influence central neuroinflammation and proteopathy. Recent mechanistic studies demonstrate that gut dysbiosis alters microbial metabolite profiles, promotes microglial immunometabolic reprogramming, and facilitates amyloid and tau pathology. The vagus nerve functions as a bidirectional conduit enabling neural transmission of inflammatory signals and tau propagation directly. Emerging evidence implicates microbiota-derived extracellular vesicles as mediators of peripheral-to-central immune modulation. Human gut-brain organoid platforms now allow causal interrogation of these interactions in physiologically relevant systems. Together, these advances reframe AD as a disorder of dysregulated neural-immune communication and identify the GBA as a tractable therapeutic target.
-
Stem Cells Expand Insights into Human Brain Evolution.
Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical progenitor proliferation may underlie cortical evolution.
-
Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke.
Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders. Loss of GABAergic interneurons after stroke may result in sensorimotor defects. Here, by transplanting human brain organoids resembling the MGE domain (human MGE organoids, hMGEOs) derived from human induced pluripotent stem cells (hiPSCs) into the infarcted cortex of stroke mice, we found that grafted hMGEOs survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time. Our study offers the feasibility of stem cell replacement therapeutics strategy for stroke.
-
[Fibro-osseous lesion of the central nervous system].
The case of a 53-year-old woman with headache and progressive right sided decline of visual acuity is reported. Computed tomography scans of the brain revealed multiple circumscribed foci of mineralization located over the left frontal and parietal, as well as the right central brain parenchyma. Surgical sampling of the left frontal lesion yielded a conglomerate composed of mineralized vessels, myriad of psammoma bodies, and metaplastic lamellar bone entangled within poorly cellular collagen fibers. No evidence was found of an underlying vascular malformation or tumor, nor was there evidence of parenchymal necrosis of infectious origin. On account of the organoid association of the mesenchymal elements and the mineralized moiety, the lesion was consistent with fibro-osseous lesion of the central nervous system. Also known as "calcifying pseudotumor" of the brain, the origin of this exceedingly rare condition is, as yet, unknown. By analogy, its pathogenesis is likely to involve mechanisms underlying tumoral calcinosis of soft tissues.
-
Beyond the neuron: the role of glial cells in viral neuropathogenesis.
The human central nervous system (CNS) is multicellular and complex. Sequelae of acute or chronic viral CNS infections can last a lifetime, and therapeutics are limited. Neurotropic viral infections can cause many manifestations, including encephalitis, meningitis, and paralysis. Most studies of neurotropic viruses focus on infection, dysfunction, and cellular death of neurons; however, neurons comprise only half of the cells of the human CNS. The remainder of the CNS is made of glial cells, such as astrocytes, microglia, oligodendrocytes, and neural progenitor cells (NPCs), which can give rise to neurons or glia. Glial cells serve critical maintenance and neuroprotective roles, including in response to infections. This review describes what is currently known about acute neurotropic viral infection of non-neuronal cells for human viral pathogens. Recent development of techniques to assess infection at the single-cell level, as well as increased complexity of human multicellular models of the brain and spinal cord, will expand our understanding of viral tropism and neuropathogenesis, potentially revealing novel therapeutic targets for these severe infections.
-
Towards correlative archaeology of the human mind.
Retracing human cognitive origins started out at the systems level with the top-down interpretation of archaeological records spanning from man-made artifacts to endocasts of ancient skulls. With emerging evolutionary genetics and organoid technologies, it is now possible to deconstruct evolutionary processes on a molecular/cellular level from the bottom-up by functionally testing archaic alleles in experimental models. The current challenge is to complement these approaches with novel strategies that allow a holistic reconstruction of evolutionary patterns across human cognitive domains. We argue that computational neuroarcheology can provide such a critical mesoscale framework at the brain network-level, linking molecular/cellular (bottom-up) to systems (top-down) level data for the correlative archeology of the human mind.
-
A Circular RNA Expressed from the FAT3 Locus Regulates Neural Development.
Circular RNAs (circRNAs) are key regulators of cellular processes, are abundant in the nervous system, and have putative regulatory roles during neural differentiation. However, the knowledge about circRNA functions in brain development is limited. Here, using RNA-sequencing, we show that circRNA levels increased substantially over the course of differentiation of human embryonic stem cells into rostral and caudal neural progenitor cells (NPCs), including three of the most abundant circRNAs, ciRS-7, circRMST, and circFAT3. Knockdown of circFAT3 during early neural differentiation resulted in minor transcriptional alterations in bulk RNA analysis. However, single-cell transcriptomics of 30 and 90 days differentiated cerebral organoids deficient in circFAT3 showed a loss of telencephalic radial glial cells and mature cortical neurons, respectively. Furthermore, non-telencephalic NPCs in cerebral organoids showed changes in the expression of genes involved in neural differentiation and migration, including FAT4, ERBB4, UNC5C, and DCC. In vivo depletion of circFat3 in mouse prefrontal cortex using in utero electroporation led to alterations in the positioning of the electroporated cells within the neocortex. Overall, these findings suggest a conserved role for circFAT3 in neural development involving the formation of anterior cell types, neuronal differentiation, or migration.
-
Human brain assembloids as a model of anaesthetic-induced neural dynamics in vitro.
BACKGROUND: The mechanisms by which anaesthetics alter neurophysiological states remain poorly understood. Although some hypotheses emphasise thalamic suppression, others propose that cortical (Cx) circuits alone, comprising interconnected excitatory and inhibitory neurones expressing gamma-aminobutyric acid type A (GABAA) receptors, are sufficient for anaesthetic-induced neural dynamics. METHODS: We generated human induced pluripotent stem cell-derived Cx-ganglionic eminence (GE) assembloids and characterised their cellular composition using immunohistochemistry and single-nucleus RNA sequencing. We recorded local field potentials and microelectrode array activity from assembloids exposed to 96 μM propofol, analysing changes in extracellular field delta power (0.1-4 Hz) and Lempel-Ziv complexity, and neuronal firing rates. Control experiments included propofol application to excitatory Cx-only organoids and co-application of propofol with the competitive GABAA receptor antagonist bicuculline. RESULTS: Cx-GE assembloids expressed propofol-sensitive GABAA receptor β2/β3 subunits on both excitatory and inhibitory neurones and chloride homeostasis machinery sufficient for hyperpolarising GABA responses. Propofol exposure significantly increased relative delta power (P=0.0078), reduced signal complexity (P=0.0117) of local field potentials, and suppressed neuronal firing rates (P=0.0156). These effects were absent in excitatory Cx-only organoids and were abolished by GABAA receptor antagonism with bicuculline, confirming the requirement for both interneurones and GABAergic signalling. Assembloids also expressed genes for neuromodulatory receptors implicated in anaesthetic emergence. CONCLUSIONS: Human Cx-GE assembloids recapitulate key electrophysiological features of anaesthetic states, demonstrating that a minimal Cx circuit containing excitatory and inhibitory neurones with functional GABAA receptors is sufficient to generate anaesthetic-induced alterations in neural dynamics. This tractable human-derived model helps disentangle Cx from subcortical contributions to anaesthesia and establishes a potential in vitro platform for mechanistic studies of anaesthetic-induced neural dynamics, drug screening, and investigation of clinically relevant individual differences in anaesthetic sensitivity, including genetic risk factors for unintentional awareness with recall and perioperative neurocognitive disorders, without the confounds of intact subcortical circuitry or the ethical constraints of human experimentation.
-
Autism Spectrum Disorder: Brain Areas Involved, Neurobiological Mechanisms, Diagnoses and Therapies.
Autism spectrum disorder (ASD), affecting over 2% of the pre-school children population, includes an important fraction of the conditions accounting for the heterogeneity of autism. The disease was discovered 75 years ago, and the present review, based on critical evaluations of the recognized ASD studies from the beginning of 1990, has been further developed by the comparative analyses of the research and clinical reports, which have grown progressively in recent years up to late 2023. The tools necessary for the identification of the ASD disease and its related clinical pathologies are genetic and epigenetic mutations affected by the specific interaction with transcription factors and chromatin remodeling processes occurring within specific complexes of brain neurons. Most often, the ensuing effects induce the inhibition/excitation of synaptic structures sustained primarily, at dendritic fibers, by alterations of flat and spine response sites. These effects are relevant because synapses, established by specific interactions of neurons with glial cells, operate as early and key targets of ASD. The pathology of children is often suspected by parents and communities and then confirmed by ensuing experiences. The final diagnoses of children and mature patients are then completed by the combination of neuropsychological (cognitive) tests and electro-/magneto-encephalography studies developed in specialized centers. ASD comorbidities, induced by processes such as anxieties, depressions, hyperactivities, and sleep defects, interact with and reinforce other brain diseases, especially schizophrenia. Advanced therapies, prescribed to children and adult patients for the control of ASD symptoms and disease, are based on the combination of well-known brain drugs with classical tools of neurologic and psychiatric practice. Overall, this review reports and discusses the advanced knowledge about the biological and medical properties of ASD.
-
FASN-dependent de novo lipogenesis is required for brain development.
Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors and reduced progenitor proliferation. Furthermore, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell-derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity in human brain organoids. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor-cell polarity and lipid metabolism.