Astrocytes and brain-derived neurotrophic factor (BDNF)

Neuroscience Research, Journal Year: 2023, Volume and Issue: 197, P. 42 - 51

Published: Feb. 11, 2023

Astrocytes are emerging in the neuroscience field as crucial modulators of brain functions, from molecular control synaptic plasticity to orchestrating brain-wide circuit activity for cognitive processes. The cellular pathways through which astrocytes modulate neuronal and quite diverse. In this review, we focus on neurotrophic pathways, mostly those mediated by brain-derived factor (BDNF). Neurotrophins a well-known family trophic factors with pleiotropic functions survival, maturation activity. Within brain, BDNF is most abundantly expressed studied all neurotrophins. While have detailed knowledge effect neurons, much less known about its physiology astroglia. However, over last years new findings emerged demonstrating that take an active part into physiology. work, discuss state-of-the-art BDNF. Indeed, sense extracellular specific TrkB receptors activate intracellular responses greatly vary depending area, stage development expressed. also uptake recycle / proBDNF at synapses contributing plasticity. Finally, experimental evidence now available describing deficits astrocytic several neuropathologies, suggesting may represent promising target clinical translation.

Language: Английский

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Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Language: Английский

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Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 286 - 286

Published: Feb. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Language: Английский

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Lipid Droplets and Neurodegeneration

Neuroscience, Journal Year: 2024, Volume and Issue: 549, P. 13 - 23

Published: May 6, 2024

Language: Английский

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Dynamics and coherence resonance in a thermosensitive neuron driven by photocurrent*

Chinese Physics B, Journal Year: 2020, Volume and Issue: 29(9), P. 098704 - 098704

Published: June 18, 2020

A feasible neuron model can be effective to estimate the mode transition in neural activities a complex electromagnetic environment. When neurons are exposed field, continuous magnetization and polarization generate nonlinear effect on exchange propagation of ions cell, then firing patterns regulated completely. The conductivity ion channels affected by temperature channel current is adjusted for regulating excitability neurons. In this paper, phototube thermistor used functions circuit. capture external illumination energy injection, signal source obtained. percept changes temperature, changed adjust neuron. This functional circuit encode heat (temperature) excitation, dynamics investigated detail. photocurrent generated as circuit, conduction dependence under effect. Bifurcation analysis Hamilton calculated explore selection. It found that complete dynamical properties biological reproduced spiking, bursting, chaotic when activated voltage source. mainly presents spiking states handled stable Gaussian white noise imposed detect occurrence coherence resonance. provide possible guidance investigating networks potential application designing sensitive sensors.

Language: Английский

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Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4705 - 4705

Published: April 29, 2021

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical genetic overlap. In up 97% of ALS cases ~50% FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which hyperphosphorylated, ubiquitinated cleaved. The TDP-43 aggregates abnormally located cytoplasm. pathogenicity cytoplasmic may be linked with both loss nuclear function gain toxic functions. cellular processes involved pathogenesis include changes RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments axonal transport autophagy, neuromuscular junctions, endoplasmic reticulum subsequent induction unfolded response. Here, we review discuss evidence for alterations these have been reported animal models proteinopathy.

Language: Английский

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Repair Mechanisms of the Neurovascular Unit after Ischemic Stroke with a Focus on VEGF

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8543 - 8543

Published: Aug. 9, 2021

The functional neural circuits are partially repaired after an ischemic stroke in the central nervous system (CNS). In CNS, neurovascular units, including neurons, endothelial cells, astrocytes, pericytes, microglia, and oligodendrocytes maintain homeostasis; however, these cellular networks damaged stroke. present review discusses repair potential of stem cells (i.e., mesenchymal precursor cells) gaseous molecules nitric oxide carbon monoxide) with respect to neuroprotection acute phase regeneration late Commonly shared molecular mechanisms unit associated vascular growth factor (VEGF) its related factors. Stem may exert therapeutic effects by diminishing VEGF-mediated leakage facilitating regenerative capacity. This presents in-depth discussion ability which endogenous produce neurons vessels capable replacing injured CNS.

Language: Английский

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Association of peripheral blood DNA methylation level with Alzheimer’s disease progression

Clinical Epigenetics, Journal Year: 2021, Volume and Issue: 13(1)

Published: Oct. 15, 2021

Abstract Background Identifying biomarkers associated with Alzheimer’s disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites AD pathology diagnosis. Here, we report relationships peripheral blood profiles measured using Infinium® MethylationEPIC BeadChip in participants from the Disease Neuroimaging Initiative (ADNI) cohort. Results The rate of cognitive decline initial sampling visit to subsequent visits was estimated by slopes modified Preclinical Alzheimer Cognitive Composite (mPACC; mPACC digit trailsB ) Clinical Dementia Rating Scale Sum Boxes (CDR-SB) plots robust linear regression cognitively normal (CN) patients mild impairment (MCI), respectively. In addition, diagnosis conversion status assessed a dichotomized endpoint. Two CpG were significantly slope CN ( P < 5.79 × 10 −8 [Bonferroni correction threshold]); cg00386386 , cg09422696 annotated RP11-661A12.5 CDR-SB. No significant identified. Genes involved cognition learning enriched. A total 19, 13, 5 differentially methylated regions (DMRs) CDR-SB, respectively, identified both comb-p DMRcate algorithms; these included DMRs HOXA4 . Furthermore, 19 MCI participants, most DMR AD-associated gene PM20D1 (chr1: 205,818,956 205,820,014 [13 probes], Sidak-corrected = 7.74 −24 ), which CDR-SB status. Conclusion Candidate as ADNI While did not identify single site sufficient utility be used itself due observed effect size, biosignature composed changes prognostic biomarker for progression.

Language: Английский

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Human iPSC-Derived Neural Models for Studying Alzheimer’s Disease: from Neural Stem Cells to Cerebral Organoids

Stem Cell Reviews and Reports, Journal Year: 2022, Volume and Issue: 18(2), P. 792 - 820

Published: Feb. 1, 2022

During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study mechanisms of human neural development, disease modeling, and drug discovery in vitro. Especially field Alzheimer's (AD), where this treatment is lacking, tremendous effort has put into investigation molecular behind using cell-based models. Numerous these studies found either novel regulatory that could be exploited develop relevant drugs for AD or already tested small molecules on vitro cultures, directly demonstrating their effect amelioration AD-associated pathology. This review thus summarizes currently differentiation strategies towards neuronal glial cell types cerebral organoids utilization modeling potential discovery.

Language: Английский

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Interlink between the gut microbiota and inflammation in the context of oxidative stress in Alzheimer’s disease progression

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: May 1, 2023

The microbiota-gut-brain axis is an important pathway of communication and may dynamically contribute to Alzheimer's disease (AD) pathogenesis. Pathological commensal gut microbiota alterations, termed as dysbiosis, can influence intestinal permeability break the blood-brain barrier which trigger AD pathogenesis via redox signaling, neuronal, immune, metabolic pathways. Dysbiosis increases oxidative stress. Oxidants affect innate immune system through recognizing microbial-derived pathogens by Toll-like receptors initiating inflammatory process. Most microbiome research work highlights relationship between AD, but contributory connection precise bacteria brain dysfunction in pathology cannot be fully demonstrated. Here, we summarize current information fundamental connections stress, inflammation, dysbiosis AD. This review emphasizes on involvement regulation responses including central peripheral cross-talk. It provides insights for novel preventative therapeutic approaches

Language: Английский

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