Microglia states and nomenclature: A field at its crossroads

Neuron, Год журнала: 2022, Номер 110(21), С. 3458 - 3483

Опубликована: Ноя. 1, 2022

Язык: Английский

---

Dysregulation of brain and choroid plexus cell types in severe COVID-19

Nature, Год журнала: 2021, Номер 595(7868), С. 565 - 571

Опубликована: Июнь 21, 2021

Язык: Английский

---

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation

Cell, Год журнала: 2022, Номер 185(14), С. 2452 - 2468.e16

Опубликована: Июнь 13, 2022

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection found white-matter-selective in mice humans. Following mild mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused neurogenesis. Concordantly, humans lasting post-COVID exhibit levels. Compared SARS-CoV-2, influenza similar patterns reactivity, oligodendrocyte loss, at early time points, but after influenza, only pathology persisted. These findings illustrate neuropathophysiology cancer therapy may contribute to impairment following even COVID.

Язык: Английский

---

The neurobiology of long COVID

Neuron, Год журнала: 2022, Номер 110(21), С. 3484 - 3496

Опубликована: Окт. 7, 2022

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 represent major component the post-acute syndrome, also known as long COVID. Here, we review what is understood about pathobiology impact on CNS discuss possible neurobiological underpinnings cognitive affecting survivors. We propose chief mechanisms that may contribute to this emerging health crisis.

Язык: Английский

---

Microglia regulate central nervous system myelin growth and integrity

Nature, Год журнала: 2022, Номер 613(7942), С. 120 - 129

Опубликована: Дек. 14, 2022

Abstract Myelin is required for the function of neuronal axons in central nervous system, but mechanisms that support myelin health are unclear. Although macrophages system have been implicated 1 , it unknown which macrophage populations involved and aspects they influence. Here we show resident microglia crucial maintenance adulthood both mice humans. We demonstrate dispensable developmental ensheathment. However, subsequent regulation growth associated cognitive function, preservation integrity by preventing its degeneration. loss due to absence with appearance a myelinating oligodendrocyte state altered lipid metabolism. Moreover, this mechanism regulated through disruption TGFβ1–TGFβR1 axis. Our findings highlight as promising therapeutic targets conditions dysregulated, such ageing neurodegenerative disease 2,3 .

Язык: Английский

---

Molecular and spatial signatures of mouse brain aging at single-cell resolution

Cell, Год журнала: 2022, Номер 186(1), С. 194 - 208.e18

Опубликована: Дек. 28, 2022

The diversity and complex organization of cells in the brain have hindered systematic characterization age-related changes its cellular molecular architecture, limiting our ability to understand mechanisms underlying functional decline during aging. Here, we generated a high-resolution cell atlas aging within frontal cortex striatum using spatially resolved single-cell transcriptomics quantified gene expression spatial major types these regions over mouse lifespan. We observed substantially more pronounced state, expression, non-neuronal neurons. Our data revealed signatures glial immune activation aging, particularly enriched subcortical white matter, identified both similarities notable differences cell-activation patterns induced by systemic inflammatory challenge. These results provide critical insights into inflammation brain.

Язык: Английский

---

Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?

The Journal of Experimental Medicine, Год журнала: 2021, Номер 218(9)

Опубликована: Июль 22, 2021

Alzheimer's disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation microglia. Because variants genes expressed in microglia correlate with AD risk, microglial response to plausibly impacts course. In mouse models, single-cell RNA sequencing (scRNA-seq) analyses delineated this as progressive conversion homeostatic into disease-associated (DAM); additional reactive populations have been reported other models neurodegeneration neuroinflammation. We review all these signatures, highlighting four fundamental patterns: DAM, IFN-microglia, MHC-II microglia, proliferating propose that are either just one or a combination, depending on the clustering strategy applied model. further single-nucleus (snRNA-seq) data from human specimens discuss reasons for parallels discrepancies between transcriptional profiles. Finally, we outline future directions delineating impact pathogenesis.

Язык: Английский

---

Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease

Nature, Год журнала: 2023, Номер 618(7964), С. 349 - 357

Опубликована: Май 31, 2023

The incidence of Alzheimer's disease (AD), the leading cause dementia, increases rapidly with age, but why age constitutes main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and structural integrity myelin sheaths1, latter which associated secondary neuroinflammation2,3. As support axonal energy metabolism neuronal health4-7, we hypothesized that loss could be an upstream for amyloid-β (Aβ) deposition, central neuropathological hallmark AD. Here identify genetic pathways dysfunction demyelinating injuries as potent drivers amyloid deposition in mouse models Mechanistically, causes accumulation Aβ-producing machinery within swellings cleavage cortical precursor protein. Suprisingly, AD mice dysfunctional lack plaque-corralling microglia despite overall increase their numbers. Bulk single-cell transcriptomics defects show there a concomitant induction highly similar distinct disease-associated signatures specific to damage plaques, respectively. Despite successful induction, (DAM) usually clear plaques are apparently distracted nearby damage. Our data suggest working model whereby age-dependent promote Aβ plaque formation directly indirectly therefore factor. Improving oligodendrocyte health promising target delay development slow progression

Язык: Английский

---

TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways

Cell, Год журнала: 2022, Номер 185(22), С. 4153 - 4169.e19

Опубликована: Окт. 1, 2022

Язык: Английский

---

Glial and myeloid heterogeneity in the brain tumour microenvironment

Nature reviews. Cancer, Год журнала: 2021, Номер 21(12), С. 786 - 802

Опубликована: Сен. 28, 2021

Язык: Английский

---