The gut microbiome modulates the transformation of microglial subtypes DOI Creative Commons
Yu Huang, Jing Wu,

Hanping Zhang

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(4), P. 1611 - 1621

Published: March 13, 2023

Abstract Clinical and animal studies have shown that gut microbiome disturbances can affect neural function behaviors via the microbiota–gut–brain axis, may be implicated in pathogenesis of several brain diseases. However, exactly how modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize cell type–specific transcriptomic changes prefrontal cortex hippocampus derived from germ-free (GF), specific pathogen free, colonized-GF mice. We found absence microbiota resulted cell-specific changes. Furthermore, microglia transcriptomes were preferentially influenced, which could effectively reversed by microbial colonization. Significantly, modulated mutual transformation microglial subpopulations two regions. Cross-species analysis showed transcriptome these mainly associated with Alzheimer’s disease (AD) major depressive disorder (MDD), further supported behavioral tests. Our findings demonstrate modulate subtypes, lead new insights into AD MDD.

Language: Английский

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation DOI Creative Commons
Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2452 - 2468.e16

Published: June 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.

Language: Английский

Citations

385
The neurobiology of long COVID DOI Creative Commons
Michelle Monje, Akiko Iwasaki

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3484 - 3496

Published: Oct. 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.

Language: Английский

Citations

297
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS DOI
Travis E. Faust, Georgia Gunner, Dorothy P. Schafer

et al.

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 657 - 673

Published: Sept. 20, 2021

Language: Английский

Citations

258
Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders DOI
Ashley N. Brandebura, Adrien Paumier, Tarik Seref Onur

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 24(1), P. 23 - 39

Published: Oct. 31, 2022

Language: Английский

Citations

257
Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer’s disease DOI Creative Commons
Jessica S. Sadick, Michael R. O’Dea, Philip Hasel

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(11), P. 1788 - 1805.e10

Published: April 4, 2022

Language: Английский

Citations

250
Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration DOI
Rickie Patani, Giles E. Hardingham, Shane A. Liddelow

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(7), P. 395 - 409

Published: June 12, 2023

Language: Английский

Citations

235
A shared disease-associated oligodendrocyte signature among multiple CNS pathologies DOI
Mor Kenigsbuch, Pierre Bost,

Shahar Halevi

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(7), P. 876 - 886

Published: June 27, 2022

Language: Английский

Citations

155
Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease DOI Open Access
Monika Piwecka, Nikolaus Rajewsky, Agnieszka Rybak‐Wolf

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(6), P. 346 - 362

Published: May 17, 2023

Language: Английский

Citations

153
Astrocytes in human central nervous system diseases: a frontier for new therapies DOI Creative Commons
Alexei Verkhratsky, Arthur M. Butt, Baoman Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

Citations

153
Specialized astrocytes mediate glutamatergic gliotransmission in the CNS DOI Creative Commons
Roberta De Ceglia, Ada Ledonne, David Litvin

et al.

Nature, Journal Year: 2023, Volume and Issue: 622(7981), P. 120 - 129

Published: Sept. 6, 2023

Abstract Multimodal astrocyte–neuron communications govern brain circuitry assembly and function 1 . For example, through rapid glutamate release, astrocytes can control excitability, plasticity synchronous activity 2,3 of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions 4–7 communicate fast focal they should possess an apparatus for Ca 2+ -dependent exocytosis similar neurons 8–10 However, the existence this mechanism has been questioned 11–13 owing inconsistent data 14–17 a lack direct supporting evidence. Here we revisited astrocyte hypothesis by considering emerging molecular heterogeneity 18–21 using molecular, bioinformatic imaging approaches, together with cell-specific genetic tools that interfere vivo. By analysing existing single-cell RNA-sequencing databases our patch-seq data, identified nine molecularly distinct clusters hippocampal astrocytes, among which found notable subpopulation selectively expressed synaptic-like glutamate-release machinery localized discrete sites. Using GluSnFR-based 22 situ vivo, corresponding subgroup responds reliably astrocyte-selective stimulations subsecond release events at spatially precise hotspots, were suppressed astrocyte-targeted deletion vesicular transporter (VGLUT1). Furthermore, or its isoform VGLUT2 revealed specific contributions glutamatergic cortico-hippocampal nigrostriatal circuits during normal behaviour pathological processes. uncovering atypical specialized adult brain, provide insights into complex roles central nervous system (CNS) physiology diseases, identify potential therapeutic target.

Language: Английский

Citations

141