Hippocampal Astrocyte Morphology Follows an Unexpected Trajectory With Age in a Transgenic Rodent Model of Tauopathy DOI Creative Commons

Emma Augustin,

Tatiana Vinasco‐Sandoval, Miriam Riquelme-Pérez

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

ABSTRACT Individual protoplasmic astrocytes have very complex and diverse spongiform shapes. The morphological diversity of is determined by the structural functional interactions astrocyte with its microenvironment. When faced pathological conditions, reorganize their morphology. Yet, little known about astrocytic response in pure tauopathies evolution over time. Here, we aimed to investigate consequences a primary neuronal tau pathology on fine morphology at three stages disease using transgenic Thy‐Tau22 mouse model. We first showed that hippocampal mice progressively accumulate hyperphosphorylated age. then developed pipeline analyses, including 3D reconstruction tdTomato‐labeled via PHP.eB adeno‐associated virus, confocal microscopy, Imaris software morphometric analysis, an advanced statistical analysis. During normal aging, complexity peaked adulthood, declined. In contrast, mice, tauopathy was associated simpler initial morphology, followed appearance cluster cells most stage. Using principal component analysis hierarchical clustering based 10 features, were able identify different morphotypes whose relative proportion varies differently age between WT mice. Interestingly, revealed fraction re‐emerges late tauopathy‐affected animals. Our data highlight concept significant reversible plasticity when chronic conditions.

Language: Английский

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

et al.

Glia, Journal Year: 2022, Volume and Issue: 70(8), P. 1467 - 1483

Published: May 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.

Language: Английский

Citations

76
A concerted neuron–astrocyte program declines in ageing and schizophrenia DOI Creative Commons
Emi Ling,

James Nemesh,

Melissa Goldman

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8004), P. 604 - 611

Published: March 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.

Language: Английский

Citations

54
Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice DOI Creative Commons
Bhanu P. Tewari, AnnaLin M. Woo, Courtney Prim

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(8), P. 1475 - 1488

Published: July 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.

Language: Английский

Citations

21
Learning-associated astrocyte ensembles regulate memory recall DOI
Michael R. Williamson, Wookbong Kwon, Junsung Woo

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Language: Английский

Citations

18
A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses DOI Creative Commons
Masaru Tanaka, László Vécsei

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1083 - 1083

Published: May 13, 2024

Welcome to

Language: Английский

Citations

17
Reactive Astrocytes and Emerging Roles in Central Nervous System (CNS) Disorders DOI
Shane A. Liddelow, Michelle L. Olsen, Michael V. Sofroniew

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(7), P. a041356 - a041356

Published: Feb. 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.

Language: Английский

Citations

16
Astrocytic modulation of neuronal signalling DOI Creative Commons

Sushmitha S. Purushotham,

Yossi Buskila

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 3

Published: June 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.

Language: Английский

Citations

29
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

et al.

Annals of the New York Academy of Sciences, Journal Year: 2023, Volume and Issue: 1525(1), P. 41 - 60

Published: May 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.

Language: Английский

Citations

24
Experience-dependent glial pruning of synaptic glomeruli during the critical period DOI Creative Commons

Nichalas Nelson,

Dominic J. Vita, Kendal Broadie

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 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.

Language: Английский

Citations

11
Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury DOI Creative Commons
Wojciech Czyżewski, Marek Mazurek, Leon Sakwa

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 12, 2024

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents central nervous system (CNS), in both pathophysiology and possible rehabilitation TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) neuroprotective (A2) phenotypes. paper elucidates interactions with neurons, their role neuroinflammation, potential for exploitation. Emphasized strategies encompass utilization endocannabinoid calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, innovative technique astrocyte transplantation as means to repair damaged neural tissues.

Language: Английский

Citations

9