The semantics of microglia activation: neuroinflammation, homeostasis, and stress

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Nov. 6, 2021

Microglia are emerging as critical regulators of neuronal function and behavior in nearly every area neuroscience. Initial reports focused on classical immune functions microglia pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions the absence disease, injury, or infection. Indeed, terms such 'microglia activation' 'neuroinflammation' used ubiquitously changes disparate contexts; particularly stress research, where prompt undue comparisons conditions. This creates a barrier for investigators new neuro-immunology ultimately hinders our understanding effects microglia. As more seek understand role neurobiology behavior, it is increasingly important develop standard methods study define microglial phenotype function. In this review, we summarize primary research physiological contexts. Further, propose framework better microglia1 chronic stress. approach will enable precise characterization different which should facilitate development microglia-directed therapeutics psychiatric neurological disease.

Language: Английский

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Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma

Science, Journal Year: 2021, Volume and Issue: 373(6553)

Published: June 3, 2021

The meninges are a membranous structure enveloping the central nervous system (CNS) that host rich repertoire of immune cells mediating CNS surveillance. Here, we report mouse contain pool monocytes and neutrophils supplied not from blood but by adjacent skull vertebral bone marrow. Under pathological conditions, including spinal cord injury neuroinflammation, CNS-infiltrating myeloid can originate brain borders display transcriptional signatures distinct their blood-derived counterparts. Thus, populated marrow niches, strategically placed to supply innate under homeostatic conditions. These findings call for reinterpretation immune-cell infiltration into during autoimmunity may inform future therapeutic approaches harness meningeal cells.

Language: Английский

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Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy

Nature, Journal Year: 2023, Volume and Issue: 615(7953), P. 668 - 677

Published: March 8, 2023

Language: Английский

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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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Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration

Immunity, Journal Year: 2022, Volume and Issue: 55(8), P. 1448 - 1465.e6

Published: Aug. 1, 2022

Language: Английский

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Emerging diagnostics and therapeutics for Alzheimer disease

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 2187 - 2199

Published: Sept. 1, 2023

Language: Английский

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Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid

Nature, Journal Year: 2022, Volume and Issue: 611(7936), P. 585 - 593

Published: Nov. 9, 2022

Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near central nervous system (CNS) parenchyma2, their role CNS physiology has not been sufficiently well studied. Given continuous interaction with cerebrospinal fluid (CSF) strategic positioning, we refer to these cells collectively as parenchymal border (PBMs). Here demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation express high levels CD163 LYVE1 (scavenger receptor proteins), closely associated brain arterial tree, show LYVE1+ motion drives flow. Pharmacological or genetic depletion led accumulation extracellular matrix proteins, obstructing access perivascular spaces impairing perfusion clearance. Ageing-associated alterations impairment dynamics were restored after intracisternal injection macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients Alzheimer's disease (AD) non-AD individuals point changes phagocytosis, endocytosis interferon-γ signalling on PBMs, pathways corroborated mouse model AD. Collectively, our results new cellular regulators dynamics, which could be targeted pharmacologically alleviate clearance deficits ageing macrophages, termed here shown fluid, implicating this cell population therapeutic targets neurological diseases such Alzheimer's.

Language: Английский

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Transforming the understanding of brain immunity

Science, Journal Year: 2023, Volume and Issue: 380(6640)

Published: April 6, 2023

Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.

Language: Английский

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Emerging roles of innate and adaptive immunity in Alzheimer’s disease

Immunity, Journal Year: 2022, Volume and Issue: 55(12), P. 2236 - 2254

Published: Nov. 8, 2022

Language: Английский

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Innate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1885 - 1885

Published: June 10, 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid β (Aβ) plaques and type 2 microtubule-associated protein (Tau) abnormalities. Multiple studies have shown that many brain’s immunological cells, specifically microglia astrocytes, are involved in AD pathogenesis. Cells innate immune system play an essential role eliminating pathogens but also regulate brain homeostasis AD. When activated, cells can cause programmed cell death through multiple pathways, including pyroptosis, apoptosis, necroptosis, PANoptosis. The often results release proinflammatory cytokines propagate response eliminate Aβ aggregated Tau proteins. However, chronic neuroinflammation, which result from death, has been linked to diseases worsen Therefore, must be tightly balanced appropriately clear these AD-related structural abnormalities without inducing neuroinflammation. In this review, we discuss responses, inflammatory cytokine secretion as they relate Therapeutic strategies targeting mechanisms will critical consider for future preventive or palliative treatments

Language: Английский

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