The Relevance of Astrocytic Cell Culture Models for Neuroinflammation in Neurodegeneration Research DOI Creative Commons

André Maciel Preato,

Ester da Silva Pinheiro, Tatiana R. Rosenstock

et al.

Neuroglia, Journal Year: 2024, Volume and Issue: 5(1), P. 27 - 49

Published: Feb. 29, 2024

Astrocytes are the predominant glial cells that provide essential support to neurons and promote microenvironment changes in neuropathological states. Astrocyte astrocytic-like cell culture have substantially contributed elucidating molecular pathways involved key roles, including those relevant neurodevelopment, brain physiology metabolism, which not readily accessible with traditional approaches. The vitro methodology has also been applied neuroinflammatory neurodegeneration contexts, revealing cellular dysfunction. studies started primary approaches using embryonic postmortem tissue. Further developments included newborn rodent cells, lines immortalized astrocytes, resulted homogeneous cell-type preparations grown on flat surfaces. To overcome some shortcomings, tridimensional bioprinted models organoid enabled mimicking of tissue arrangements and, above these achievements, complex astrocyte can be generated from induced pluripotent stem (iPSCs) model diseases. These unprecedented breakthroughs allowed development platforms test new therapies derived human material noninvasively obtained live patients. In this work, we reviewed most studied astrocytic for discussing limitations, advantages reliable experimental readouts neuroinflammation research.

Language: Английский

The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications DOI Open Access
Sehwan Kim, Un Ju Jung, Sang Ryong Kim

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

Citations

5

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

Inflammaging and Brain Aging DOI Open Access
Maria Carolina Jurcău, Anamaria Jurcău,

Alexander Cristian

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10535 - 10535

Published: Sept. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Language: Английский

Citations

9

Characterization of human iPSC-derived astrocytes with potential for disease modeling and drug discovery DOI Creative Commons
Vincent Soubannier, Gilles Maussion, Mathilde Chaineau

et al.

Neuroscience Letters, Journal Year: 2020, Volume and Issue: 731, P. 135028 - 135028

Published: May 4, 2020

Astrocytes play a number of key functions in health and disease. Activated astrocytes are present most, if not all, neurological diseases. Most current information on the mechanisms underlying reactive astrocyte emergence derives from studies using animal experimental systems, mainly because ability to study human under healthy pathological conditions has been hampered by difficulty obtaining primary astrocytes. Here we describe robust reliable derivation induced pluripotent stem cells (iPSCs). Phenotypically characterized iPSC-derived exhibit typical traits physiological astrocytes, including spontaneous calcium transients. Moreover, respond stimulation with pro-inflammatory combination tumor necrosis factor-alpha, interleukin 1-alpha, complement component C1q undergoing changes gene expression patterns suggesting acquisition phenotype. Together, these findings provide evidence that suitable model system function reactivation nervous system.

Language: Английский

Citations

54

Sodium Butyrate and Indole-3-propionic Acid Prevent the Increase of Cytokines and Kynurenine Levels in LPS-induced Human Primary Astrocytes DOI Open Access
Michelle Lima Garcez, Vanessa Tan, Benjamin Heng

et al.

International Journal of Tryptophan Research, Journal Year: 2020, Volume and Issue: 13

Published: Jan. 1, 2020

The crosstalk between central nervous system (CNS) and gut microbiota plays key roles in neuroinflammation chronic immune activation that are common features of all neurodegenerative diseases. Imbalance the can lead to an increase intestinal permeability allowing toxins diffuse reach CNS, as well impairing production neuroprotective metabolites such sodium butyrate (SB) indole-3-propionic acid (IPA). aim present study was evaluate effect SB IPA on LPS-induced cytokines tryptophan human astrocytes. Primary cultures astrocytes were pre-incubated with or for 1 hour before treatment LPS. Cell viability not affected at 24, 48 72 hours after pre-treatment SB, LPS treatment. able significantly prevent GM-CSF, MCP-1, IL-6 IL-12, IL-13 triggered by also prevented inflammation indicated kynurenine kynurenine/tryptophan ratio induced IL-13, TNF-α levels 24 pre-treatment, but had no metabolites. showed first time bacterial have potential anti-inflammatory primary therapeutic benefit disease characterized presence low-grade inflammation.

Language: Английский

Citations

51

Contribution of senescent and reactive astrocytes on central nervous system inflammaging DOI

Michel López-Teros,

Adriana Alarcón‐Aguilar, Norma Edith López‐Díazguerrero

et al.

Biogerontology, Journal Year: 2022, Volume and Issue: 23(1), P. 21 - 33

Published: Jan. 27, 2022

Language: Английский

Citations

22

Expression and mechanisms of interferon-stimulated genes in viral infection of the central nervous system (CNS) and neurological diseases DOI Creative Commons

Rui Lang,

Huiting Li,

Xiaoqin Luo

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 17, 2022

Interferons (IFNs) bind to cell surface receptors and activate the expression of interferon-stimulated genes (ISGs) through intracellular signaling cascades. ISGs their products have various biological functions, such as antiviral immunomodulatory effects, are essential effector molecules for IFN function. limit invasion replication virus in a cell-specific region-specific manner central nervous system (CNS). In addition participating natural immunity against viral infections, studies shown that pathogenesis CNS disorders neuroinflammation neurodegenerative diseases. The aim this review is present macroscopic overview characteristics restrict neural underlying infection cells. Furthermore, we elucidate neurological inflammation, neuropsychiatric depression well disorders, including Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS). Finally, summarize several (ISG15, IFIT2, IFITM3) been studied more recent years research progress

Language: Английский

Citations

20

Antidepressant mechanisms of ketamine’s action: NF-κB in the spotlight DOI
Paulina Sokołowska, Michał Seweryn Karbownik, Marta Jóźwiak-Bębenista

et al.

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 218, P. 115918 - 115918

Published: Nov. 10, 2023

Language: Английский

Citations

11

Cytokine profiling in senescent and reactive astrocytes: A systematic review DOI

Michel López-Teros,

Adriana Alarcón‐Aguilar,

Alejandra Castillo-Aragón

et al.

Neurobiology of Aging, Journal Year: 2024, Volume and Issue: 138, P. 28 - 35

Published: Feb. 27, 2024

Language: Английский

Citations

4

Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes DOI Creative Commons
Josephine L. Robb, Nicole A. Morrissey, Paul G. Weightman Potter

et al.

Neuroscience, Journal Year: 2019, Volume and Issue: 447, P. 167 - 181

Published: Nov. 22, 2019

Chronic low-grade inflammation is a feature of the pathophysiology obesity and diabetes in CNS as well peripheral tissues. Glial cells are critical mediators response to brain. Key features glia include their metabolic flexibility, sensitivity changes microenvironment, ability rapidly adapt function accordingly. They specialised which cooperate promote preserve neuronal health, playing important roles regulating activity networks across brain during different life stages. Increasing evidence points role glia, most notably astrocytes microglia, systemic regulation energy glucose homeostasis course normal physiological control disease. Inflammation an energetically expensive process that requires adaptive cellular metabolism and, turn, intermediates can also have immunomodulatory actions. Such "immunometabolic" immune been implicated contributing disease pathology diabetes. This review will discuss for immunometabolic glial homeostasis, how this context

Language: Английский

Citations

35