Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Stress induced microglial activation contributes to depression

Pharmacological Research, Journal Year: 2022, Volume and Issue: 179, P. 106145 - 106145

Published: Feb. 24, 2022

Language: Английский

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Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells

Glia, Journal Year: 2023, Volume and Issue: 71(6), P. 1383 - 1401

Published: Feb. 17, 2023

Abstract The mammalian brain is a complex organ comprising neurons, glia, and more than 1 × 10 14 synapses. Neurons are heterogeneous group of electrically active cells, which form the framework circuitry brain. However, glial primarily divided into astrocytes, microglia, oligodendrocytes (OLs), oligodendrocyte precursor cells (OPCs), constitute approximately half all neural in central nervous system (CNS) mainly provide nutrition tropic support to neurons In last two decades, concept “tripartite synapses” has drawn great attention, emphasizes that astrocytes an integral part synapse regulate neuronal activity feedback manner after receiving signals. Since then, synaptic modulation by been extensively studied substantially revised. this review, we summarize latest significant findings on how particular, microglia OL lineage impact remodel structure function synapses Our review highlights cellular molecular aspects neuron‐glia crosstalk provides additional information aberrant communication between glia may contribute pathologies.

Language: Английский

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Syncytial nerve net in a ctenophore adds insights on the evolution of nervous systems

Science, Journal Year: 2023, Volume and Issue: 380(6642), P. 293 - 297

Published: April 20, 2023

A fundamental breakthrough in neurobiology has been the formulation of neuron doctrine by Santiago Ramón y Cajal, which stated that nervous system is composed discrete cells. Electron microscopy later confirmed and allowed identification synaptic connections. In this work, we used volume electron three-dimensional reconstructions to characterize nerve net a ctenophore, marine invertebrate belongs one earliest-branching animal lineages. We found neurons subepithelial have continuous plasma membrane forms syncytium. Our findings suggest differences architectures between ctenophores cnidarians or bilaterians offer an alternative perspective on neural network organization neurotransmission.

Language: Английский

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Exploring the Role of Neuroplasticity in Development, Aging, and Neurodegeneration

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(12), P. 1610 - 1610

Published: Nov. 21, 2023

Neuroplasticity refers to the ability of brain reorganize and modify its neural connections in response environmental stimuli, experience, learning, injury, disease processes. It encompasses a range mechanisms, including changes synaptic strength connectivity, formation new synapses, alterations structure function neurons, generation neurons. plays crucial role developing maintaining function, learning memory, as well recovery from injury adaptation changes. In this review, we explore vast potential neuroplasticity various aspects across lifespan context disease. Changes aging significance cognitive later life will also be reviewed. Finally, discuss common mechanisms associated with age-related neurodegenerative processes (including protein aggregation accumulation, mitochondrial dysfunction, oxidative stress, neuroinflammation) how these can mitigated, at least partially, by non-invasive non-pharmacologic lifestyle interventions aimed promoting harnessing neuroplasticity.

Language: Английский

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Aging microglia

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(5)

Published: April 21, 2023

Abstract Microglia are the tissue-resident macrophage population of brain, specialized in supporting CNS environment and protecting it from endogenous exogenous insults. Nonetheless, their function declines with age, ways that remain to be fully elucidated. Given critical role played by microglia neurodegenerative diseases, a better understanding aging phenotype is an essential prerequisite designing preventive therapeutic strategies. In this review, we discuss most recent literature on aging, comparing findings rodent models human subjects.

Language: Английский

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Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(6), P. 1075 - 1086

Published: April 22, 2024

Abstract Human brain organization involves the coordinated expression of thousands genes. For example, first principal component (C1) cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing Allen Brain Atlas revealed two new components gene architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic immune processes, specific cell types cytoarchitectonics, genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Cell BrainSpan), we found that C1–C3 represent generalizable transcriptional programs within cells differentially phased during fetal postnatal development. Autism spectrum disorder schizophrenia were specifically C1/C2 respectively, across neuroimaging, differential genome-wide studies. Evidence converged especially in support C3 as normative program adolescent development, can lead atypical supragranular connectivity people at high risk schizophrenia.

Language: Английский

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Microglia as integrators of brain-associated molecular patterns

Trends in Immunology, Journal Year: 2024, Volume and Issue: 45(5), P. 358 - 370

Published: April 23, 2024

Language: Английский

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Microglial efferocytosis: Diving into the Alzheimer’s disease gene pool

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3513 - 3533

Published: Nov. 1, 2022

Genome-wide association studies and functional genomics have linked specific cell types, genes, pathways to Alzheimer's disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, thus activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) etiology AD. These converge on (endocytosis/phagocytosis, cholesterol metabolism, immune response) with critical roles core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting relevant identified latest genetics studies, describe how they may contribute pathogenesis. Investigating impact AD-associated variants is essential for elucidating mechanisms developing effective therapeutic approaches.

Language: Английский

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The Role of Osteopontin in Microglia Biology: Current Concepts and Future Perspectives

Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 840 - 840

Published: April 3, 2022

The innate immune landscape of the central nervous system (CNS), including brain and retina, consists different myeloid cell populations with distinct tasks to fulfill. Whereas CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is build up a defense against invading pathogens other damaging factors from periphery, resident cells parenchyma microglia, are highly dynamic plethora functions during homeostasis disease. Therefore, microglia constantly sensing their environment closely interacting surrounding cells, which in part mediated by soluble factors. One these Osteopontin (OPN), multifunctional protein that produced types CNS, upregulated neurodegenerative neuroinflammatory conditions. In this review, we discuss current literature about interaction between OPN several disease entities, multiple sclerosis (MS), Alzheimer's cerebrovascular diseases (AD, CVD), amyotrophic lateral (ALS), age-related macular degeneration (AMD) diabetic retinopathy (DR), context molecular pathways involved signaling shaping function microglia. As nearly all characterized pathological alterations microglial accompanied disturbance homeostatic phenotype, emergence disease-associated (DAM) states interplay DAM-signature, such as OPN, great interest for therapeutical interventions future.

Language: Английский

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