Emerging evidence of context-dependent synapse elimination by phagocytes in the CNS DOI
Fang-Shuai Shen, Cui Liu,

Hui-Zhe Sun

и другие.

Journal of Leukocyte Biology, Год журнала: 2024, Номер 116(3), С. 511 - 522

Опубликована: Май 3, 2024

Abstract Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune nutrition support, recent groundbreaking studies have revealed that phagocytic microglia astrocytes can actively selectively eliminate synapses normal diseased brains, thereby mediating loss maintaining homeostasis. Multiple lines evidence indicate mechanisms by glia are not universal but rather depend on specific contexts detailed neuron–glia interactions. The mechanism dependent neuron-intrinsic factors many innate local apoptosis-related molecules. During development, microglial engulfment visual thalamus primarily influenced classic complement pathway, whereas barrel cortex, fractalkine pathway dominant. In Alzheimer's disease, employ complement-dependent tauopathy early β-amyloid pathology, involved at late stages. Phagocytic also engulf way schizophrenia, anxiety, stress. addition, MEGF10-dependent memory, stroke. Furthermore, phenomenon phagocytes excitatory inhibitory emphasized this review. We hypothesize elucidating context-dependent may reveal molecular basis disorders provide rationale developing novel candidate therapies target

Язык: Английский

The role of astrocyte structural plasticity in regulating neural circuit function and behavior DOI
Oluwadamilola O. Lawal, Francesco Paolo Ulloa Severino, Çağla Eroğlu

и другие.

Glia, Год журнала: 2022, Номер 70(8), С. 1467 - 1483

Опубликована: Май 10, 2022

Abstract Brain circuits undergo substantial structural changes during development, driven by the formation, stabilization, and elimination of synapses. Synaptic connections continue to experience‐dependent rearrangements throughout life, which are postulated underlie learning memory. Astrocytes, a major glial cell type in brain, physically contact with synaptic through their ensheathment Astrocytes strongly contribute remodeling structures healthy diseased central nervous systems regulating connectivity behaviors. However, whether plasticity astrocytes is involved critical functions at synapse unknown. This review will discuss emerging evidence linking astrocytic circuit regulation Moreover, we survey possible molecular cellular mechanisms non‐cell‐autonomous effects on neuronal plasticity. Finally, how astrocyte morphological different physiological states disease conditions function dysfunction.

Язык: Английский

Процитировано

77
A concerted neuron–astrocyte program declines in ageing and schizophrenia DOI Creative Commons
Emi Ling,

James Nemesh,

Melissa Goldman

и другие.

Nature, Год журнала: 2024, Номер 627(8004), С. 604 - 611

Опубликована: Март 6, 2024

Abstract Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people’s cortical neurons astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22–97 years, including healthy individuals with schizophrenia. Latent-factor analysis these data revealed that, whose more strongly expressed genes encoding synaptic components, astrocytes distinct functions for synthesizing cholesterol, an astrocyte-supplied component membranes. call this neuron astrocyte program (SNAP). In schizophrenia ageing—two conditions that involve declines cognitive flexibility plasticity 1,2 —cells divested from SNAP: astrocytes, glutamatergic (excitatory) GABAergic (inhibitory) all showed reduced SNAP expression corresponding degrees. The astrocytic neuronal components both involved which genetic risk factors were concentrated. SNAP, varies quantitatively even among similar age, may underlie many aspects normal interindividual differences be important point convergence multiple kinds pathophysiology.

Язык: Английский

Процитировано

56
Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice DOI Creative Commons
Bhanu P. Tewari, AnnaLin M. Woo, Courtney Prim

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(8), С. 1475 - 1488

Опубликована: Июль 17, 2024

Abstract Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show terminals interneurons localize to holes in adult mouse somatosensory cortex. Approximately 95% contain and astrocytic processes expressing Kir4.1, glutamate GABA transporters. Hence, tripartite synapses. In brain, PNN degradation causes an expanded coverage neuronal somata without altering axon terminals. The loss impairs transmitter potassium uptake, resulting spillage into extrasynaptic space. Our data astrocytes cooperate synaptically released signals physiological conditions. Their combined action is altered models Alzheimer’s disease epilepsy where disrupted.

Язык: Английский

Процитировано

23
Learning-associated astrocyte ensembles regulate memory recall DOI
Michael R. Williamson, Wookbong Kwon, Junsung Woo

и другие.

Nature, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Язык: Английский

Процитировано

21
A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses DOI Creative Commons
Masaru Tanaka, László Vécsei

Biomedicines, Год журнала: 2024, Номер 12(5), С. 1083 - 1083

Опубликована: Май 13, 2024

Welcome to

Язык: Английский

Процитировано

18
Astrocytic modulation of neuronal signalling DOI Creative Commons

Sushmitha S. Purushotham,

Yossi Buskila

Frontiers in Network Physiology, Год журнала: 2023, Номер 3

Опубликована: Июнь 1, 2023

Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.

Язык: Английский

Процитировано

32
Astrocytes as master modulators of neural networks: Synaptic functions and disease‐associated dysfunction of astrocytes DOI Creative Commons
Jeffrey A. Stogsdill, Corey C. Harwell, Steven A. Goldman

и другие.

Annals of the New York Academy of Sciences, Год журнала: 2023, Номер 1525(1), С. 41 - 60

Опубликована: Май 23, 2023

Abstract Astrocytes are the most abundant glial cell type in central nervous system and essential to development, plasticity, maintenance of neural circuits. heterogeneous, with their diversity rooted developmental programs modulated by local brain environment. play integral roles regulating coordinating activity extending far beyond metabolic support neurons other phenotypes. Both gray white matter astrocytes occupy critical functional niches capable modulating physiology on time scales slower than synaptic but faster those adaptive responses requiring a structural change or myelination. Given many associations roles, it is not surprising that astrocytic dysfunction has been causally implicated broad set neurodegenerative neuropsychiatric disorders. In this review, we focus recent discoveries concerning contributions function networks, dual contribution development maturation, role supporting myelin integrity, hence conduction its regulation. We then address emerging disease pathogenesis potential strategies for targeting these cells therapeutic purposes.

Язык: Английский

Процитировано

25
Reactive Astrocytes and Emerging Roles in Central Nervous System (CNS) Disorders DOI
Shane A. Liddelow, Michelle L. Olsen, Michael V. Sofroniew

и другие.

Cold Spring Harbor Perspectives in Biology, Год журнала: 2024, Номер 16(7), С. a041356 - a041356

Опубликована: Фев. 5, 2024

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is heterogeneous spectrum of potential changes occur context-specific manner. These are determined by diverse signaling events vary not only with nature severity different insults but also location CNS, genetic predispositions, age, potentially "molecular memory" previous events. Astrocyte can be associated both essential beneficial as well harmful effects. The available information rapidly expanding much has been learned about molecular diversity reactivity. Emerging functional associations point toward roles for determining outcome disorders.

Язык: Английский

Процитировано

17
Experience-dependent glial pruning of synaptic glomeruli during the critical period DOI Creative Commons

Nichalas Nelson,

Dominic J. Vita, Kendal Broadie

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 20, 2024

Abstract Critical periods are temporally-restricted, early-life windows when sensory experience remodels synaptic connectivity to optimize environmental input. In the Drosophila juvenile brain, critical period drives synapse elimination, which is transiently reversible. Within olfactory neuron (OSN) classes synapsing onto single projection neurons extending brain learning/memory centers, we find glia mediate experience-dependent pruning of OSN glomeruli downstream odorant exposure. We glial projections infiltrate neuropil in response experience, and use Draper (MEGF10) engulfment receptors prune glomeruli. Downstream, antagonistic Basket (JNK) Puckered (DUSP) signaling required for translocation activated into nuclei. Dependent on this signaling, expression F-actin linking scaffold Cheerio (FLNA), absolutely essential pruning. mediates regulation cytoskeleton remodeling. These results define a sequential pathway strictly-defined period; input infiltration projections, Draper/MEGF10 activate Basket/JNK cascade transcriptional activation, Cheerio/FLNA induction regulates actin targeted phagocytosis.

Язык: Английский

Процитировано

11
Astrocyte-Mediated Neuroinflammation in Neurological Conditions DOI Creative Commons
Yanxiang Zhao, Yingying Huang,

Ying Cao

и другие.

Biomolecules, Год журнала: 2024, Номер 14(10), С. 1204 - 1204

Опубликована: Сен. 25, 2024

Astrocytes are one of the key glial types central nervous system (CNS), accounting for over 20% total cells in brain. Extensive evidence has established their indispensable functions maintenance CNS homeostasis, as well broad involvement neurological conditions. In particular, astrocytes can participate various neuroinflammatory processes, e.g., releasing a repertoire cytokines and chemokines or specific neurotrophic factors, which result both beneficial detrimental effects. It become increasingly clear that such astrocyte-mediated neuroinflammation, together with its complex crosstalk other immune cells, designates neuronal survival functional integrity neurocircuits, thus critically contributing to disease onset progression. this review, we focus on current knowledge responses astrocytes, summarizing common features Moreover, highlight several vital questions future research promise novel insights into diagnostic therapeutic strategies against those debilitating diseases.

Язык: Английский

Процитировано

11