Early-life stress induces persistent astrocyte dysfunction resulting in fear generalisation DOI Open Access

Mathias Guayasamin,

Lewis R Depaauw-Holt,

Ifeoluwa I Adedipe

et al.

Published: Aug. 6, 2024

Early-life stress can have lifelong consequences, enhancing susceptibility and resulting in behavioral cognitive deficits. While the effects of early-life on neuronal function been well-described, we still know very little about contribution non-neuronal brain cells. Investigating complex interactions between distinct cell types is critical to fully understand how cellular changes manifest as deficits following stress. Here, using male female mice report that induces anxiety-like behavior fear generalisation an amygdala-dependent learning memory task. These were associated with impaired synaptic plasticity, increased neural excitability, astrocyte dysfunction. Genetic perturbation amygdala by either silencing these cells or reducing network was sufficient replicate cellular, synaptic, data provide mechanistic links Our reveal a role astrocytes tuning emotionally salient dysfunction generalisation. Further understanding are affected might offer new insights into long-term impact affective states.

Language: Английский

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders DOI Creative Commons

Yejia Xu,

Bowen Jia,

Jing Li

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

Citations

18
Astrocyte ensembles manipulated with AstroLight tune cue-motivated behavior DOI
Irene Serra, C. Martín, Javier Sánchez Romero

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Language: Английский

Citations

2
Astrocytes in selective vulnerability to neurodegenerative disease DOI Creative Commons
Till S. Zimmer, Adam L. Orr, Anna G. Orr

et al.

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(4), P. 289 - 302

Published: March 22, 2024

Selective vulnerability of specific brain regions and cell populations is a hallmark neurodegenerative disorders. Mechanisms selective involve neuronal heterogeneity, functional specializations, differential sensitivities to stressors pathogenic factors. In this review we discuss the growing body literature suggesting that, like neurons, astrocytes are heterogeneous specialized, respond integrate diverse inputs, induce effects on function. disease, undergo specific, context-dependent changes that promote different trajectories outcomes. We propose contribute through maladaptive transitions context-divergent phenotypes impair functions. Further studies multifaceted roles in disease may provide new therapeutic approaches enhance resilience against

Language: Английский

Citations

14
Norepinephrine Signals Through Astrocytes To Modulate Synapses DOI Creative Commons

Katheryn B. Lefton,

Yifan Wu, Allen Yen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 22, 2024

Abstract Locus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors Ca 2+ dynamics fully gate effect synapses as astrocyte-specific deletion three astrocyte-silencing approaches all render insensitive NE. Additionally, find suppression strength results an ATP-derived adenosine A1 receptor-mediated control presynaptic efficacy. An accompanying study Chen et al. reveals existence analogous pathway in larval zebrafish highlights importance state transitions. Together, these findings fuel a new model wherein astrocytes core component neuromodulatory systems effector through which produces adaptations, challenging 80-year-old status quo.

Language: Английский

Citations

9
Efficient Gene Delivery Admitted by small Metabolites Specifically Targeting Astrocytes in the Mouse Brain DOI

Haibin Zhou,

Jiajing Dai,

Dong Li

et al.

Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 1166 - 1179

Published: Jan. 11, 2025

Language: Английский

Citations

1
Astrocytic GABAergic Regulation in Alcohol Use and Major Depressive Disorders DOI Creative Commons
Dina Ali, H. Mokdad Ali, Matthew R. Lopez

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 318 - 318

Published: Feb. 9, 2024

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in central nervous system (CNS). Most GABAergic neurons synthesize GABA from glutamate and release it synaptic cleft CNS. However, astrocytes can also GABA, activating receptors neighboring physiological pathological conditions. As primary homeostatic glial cells brain, play a crucial role regulating homeostasis neurotransmission. Accumulating evidence demonstrates that astrocytic dysregulation implicated psychiatric disorders, including alcohol use disorder (AUD) depressive (MDD), most prevalent co-occurring disorders. Several current medications emerging pharmacological agents targeting levels are clinical trials for treating AUD MDD. This review offers concise summary of regulation We provide an overview understanding areas debate regarding mechanisms by which regulate CNS their potential significance molecular basis MDD, paving way toward future research directions therapeutic target within this field.

Language: Английский

Citations

6
Neuron–Glial Interactions: Implications for Plasticity, Behavior, and Cognition DOI
Mauricio Rangel‐Gomez, Cristina M. Alberini,

Benjamin Deneen

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(40), P. e1231242024 - e1231242024

Published: Oct. 2, 2024

The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, include a diversity other functions, such regulation complex behaviors. Astrocytes, the most abundant central nervous system (CNS), have been shown modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling behavioral functions. Contemporary studies further highlight astrocytes’ involvement cognitive For instance, inhibiting astrocytes hippocampus can lead memory deficits, suggesting their integral role processes. Moreover, astrocytic calcium activity astrocyte–neuron metabolic coupling linked changes strength learning. Microglia, another type cell, also extend beyond roles, contributing learning processes, with microglial reductions impacting these developmentally dependent manner. Oligodendrocytes, traditionally thought limited roles postdevelopment, are now recognized for activity-dependent modulation myelination plasticity, thus responses. Recent advancements computational modeling expanded our understanding particularly how influence circuits This review underscores importance CNS need research unravel complexities neuron–glia interactions, impact interactions on brain potential implications neurological diseases.

Language: Английский

Citations

5
Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation DOI Open Access

Mathias Guayasamin,

Lewis R Depaauw-Holt,

Ifeoluwa I Adedipe

et al.

Published: Jan. 15, 2025

Early-life stress can have lifelong consequences, enhancing susceptibility and resulting in behavioural cognitive deficits. While the effects of early-life on neuronal function been well-described, we still know very little about contribution non-neuronal brain cells. Investigating complex interactions between distinct cell types is critical to fully understand how cellular changes manifest as deficits following stress. Here, using male female mice report that induces anxiety-like behaviour fear generalisation an amygdala-dependent learning memory task. These were associated with impaired synaptic plasticity, increased neural excitability, astrocyte hypofunction. Genetic perturbation amygdala by either reducing calcium activity or network was sufficient replicate cellular, synaptic, Our data reveal a role astrocytes tuning emotionally salient provide mechanistic links stress, hypofunction,

Language: Английский

Citations

0
Astrocyte-Secreted Lcn2 Modulates Dendritic Spine Morphology DOI Creative Commons
Marta Doliwa, Bożena Kuźniewska, Karolina Nader

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 159 - 159

Published: Jan. 21, 2025

Learning and memory formation rely on synaptic plasticity, the process that changes strength in response to neuronal activity. In tripartite synapse concept, molecular signals affect morphology originate not only from pre- post-synaptic terminals but also astrocytic processes ensheathing many synapses. Despite significant progress made understanding contribution a few plasticity-related proteins have been identified so far. this study, we present evidence indicating role of astrocyte-secreted Lipocalin-2 (Lcn2) plasticity. We show Lcn2 expression is induced hippocampal astrocytes kainate-evoked aberrant plasticity model. Next, demonstrate chemically long-term potentiation (cLTP) similarly increases neuronal–glial co-cultures, glutamate causes immediate release these cultures. Additionally, through experiments primary cultures, reveal triggered by calcium signaling, brief treatment co-cultures with alters dendritic spines. Based findings, propose as an activity-dependent molecule released influences spine morphology.

Language: Английский

Citations

0
Unveiling the functional connectivity of astrocytic networks with AstroNet, a graph reconstruction algorithm coupled to image processing DOI Creative Commons
Lou Zonca,

Félix Bellier,

Giampaolo Milior

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 24, 2025

Astrocytes form extensive networks with diverse calcium activity, yet the organization and connectivity of these across brain regions remain largely unknown. To address this, we developed AstroNet, a data-driven algorithm that uses two-photon imaging to map temporal correlations in astrocyte activation. By organizing individual activation events chronologically, our method reconstructs functional extracts local correlations. We create graph network by tallying direct co-activations between pairs cells along pathways. Applied CA1 hippocampus motor cortex, AstroNet reveals notable differences: astrocytes display stronger connectivity, while cortical sparser networks. In both regions, smaller, tightly connected sub-networks are embedded within larger, loosely structure. This not only identifies paths but also distinct, region-specific patterns, providing new insights into astrocytic brain. novel algorithm, maps through imaging, revealing distinct patterns regions.

Language: Английский

Citations

0