Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?

Trends in Immunology, Год журнала: 2020, Номер 41(9), С. 820 - 835

Опубликована: Авг. 17, 2020

Язык: Английский

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A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation

Journal of Neuroinflammation, Год журнала: 2020, Номер 17(1)

Опубликована: Май 11, 2020

Interactions between neurons, astrocytes, and microglia critically influence neuroinflammatory responses to insult in the central nervous system. In vitro astrocyte cultures are powerful tools study specific molecular pathways involved neuroinflammation; however, order better understand of cellular crosstalk on neuroinflammation, new multicellular culture models required.Primary cortical cells taken from neonatal rats were cultured a serum-free "tri-culture" medium formulated support microglia, or "co-culture" only neurons astrocytes. Caspase 3/7 activity morphological changes used quantify response two types different stimuli mimicking sterile bacterial infection (lipopolysaccharide (LPS) exposure), mechanical injury (scratch), seizure (glutamate-induced excitotoxicity). The secreted cytokine profile control LPS-exposed co- tri-cultures also compared.The tri-culture maintained physiologically relevant representation for 14 days vitro, while co-cultures similar population but lacked microglia. continuous presence did not negatively impact overall health tri-culture, which showed reduced caspase neurite outgrowth as co-cultures, along with an increase microglia-secreted neurotrophic factor IGF-1 significantly concentration CX3CL1 conditioned media. significant hypertrophy, activity, secretion number pro-inflammatory cytokines (e.g., TNF, IL-1α, IL-1β, IL-6), none observed co-cultures. Following trauma, increased compared co-culture, migration towards source injury. Finally, played neuroprotective role during glutamate-induced excitotoxicity, neuron loss hypertrophy tri-culture.The consisting more faithfully mimics vivo than standard mono- This can be useful tool neuroinflammation improved accuracy predicting phenomena.

Язык: Английский

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Astrocyte-immune cell interactions in physiology and pathology

Immunity, Год журнала: 2021, Номер 54(2), С. 211 - 224

Опубликована: Фев. 1, 2021

Язык: Английский

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Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Ноя. 27, 2023

As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks premature death other medical conditions for patients. Neuroinflammation is abnormal immune response in brain, its correlation with MDD receiving increasing attention. has been reported to be involved through distinct neurobiological mechanisms, among which dysregulation neurogenesis dentate gyrus (DG) hippocampus (HPC) The DG two niches adult mammalian neurotrophic factors are fundamental regulators this process. cell types mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, peripheral cells selectively penetrate blood-brain barrier infiltrate into inflammatory regions. This review summarizes functions affected by during progression corresponding influences on memory patients model animals.

Язык: Английский

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Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16288 - 16288

Опубликована: Ноя. 14, 2023

The blood-brain barrier (BBB) is a unique and selective feature of the central nervous system's vasculature. BBB dysfunction has been observed as an early sign Alzheimer's Disease (AD) before onset dementia or neurodegeneration. intricate relationship between pathogenesis AD, especially in context neurovascular coupling overlap pathophysiology neurodegenerative cerebrovascular diseases, underscores urgency to understand BBB's role more deeply. Preserving restoring function emerges potentially promising strategy for mitigating progression severity AD. Molecular genetic changes, such isoform ε4 apolipoprotein E (ApoEε4), significant risk factor promoter dysfunction, have shown mediate disruption. Additionally, receptors transporters like low-density lipoprotein receptor-related protein 1 (LRP1), P-glycoprotein (P-gp), receptor advanced glycation end products (RAGEs) implicated AD's pathogenesis. In this comprehensive review, we endeavor shed light on pathogenic therapeutic connections AD BBB. We also delve into latest developments pioneering strategies targeting interventions, addressing its potential carrier. By providing integrative perspective, anticipate paving way future research treatments focused exploiting therapy.

Язык: Английский

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Molecular and metabolic heterogeneity of astrocytes and microglia

Cell Metabolism, Год журнала: 2023, Номер 35(4), С. 555 - 570

Опубликована: Март 22, 2023

Язык: Английский

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Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease

Journal of Neurochemistry, Год журнала: 2021, Номер 164(3), С. 309 - 324

Опубликована: Дек. 21, 2021

Abstract Astrocytes are highly efficient homeostatic glial cells playing a crucial role in optimal brain functioning and homeostasis. respond to changes homoeostasis following central nervous system (CNS) injury/diseased state by specific defence mechanism called reactive astrogliosis. Recent studies have implicated placed astrogliosis the centre of pathophysiology Alzheimer's disease (AD) other neurodegenerative disorders. The AD biomarker field is evolving rapidly with new findings providing strong evidence which supports notion that an early event time course progression may precede pathological hallmarks AD. Clinical/translational vivo PET vitro postmortem imaging demonstrated ‘a first second wave’ distinct close‐loop relationships biomarkers at different stages disease. At end stages, astrocytes found be associated, or proximity, amyloid plaque tau deposits brains. Several PET‐tracers, being pipeline validated very fast pace for mapping visualising brain, will provide further invaluable mechanistic insights into non‐AD dementia pathologies. complementary roles microglia astrocyte activation progression, along clinical value fluid context existing biomarkers, latest avenue needs exploration.

Язык: Английский

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Dopamine: an immune transmitter

Neural Regeneration Research, Год журнала: 2020, Номер 15(12), С. 2173 - 2173

Опубликована: Янв. 1, 2020

The dopaminergic system controls several vital central nervous functions, including the control of movement, reward behaviors and cognition. Alterations signaling are involved in pathogenesis neurodegenerative psychiatric disorders, particular Parkinson’s disease, which associated with a subtle chronic inflammatory response. A substantial body evidence has demonstrated non-neuronal expression dopamine, its receptors machinery that governs synthesis, secretion storage dopamine across immune cell types. This review aims to summarize current knowledge on role cells. One goals is decipher complex mechanisms through these types respond order address impact this pathologies such as disease. further aim illustrate gaps our understanding physiological roles encourage more targeted research focused consequences aberrant production regulation. These highlights may prompt scientists field consider alternative functions important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.

Язык: Английский

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Astrocyte Diversity: Current Insights and Future Directions

Neurochemical Research, Год журнала: 2020, Номер 45(6), С. 1298 - 1305

Опубликована: Янв. 31, 2020

Язык: Английский

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Microglia and astrocyte involvement in neurodegeneration and brain cancer

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Дек. 1, 2021

The brain is unique and the most complex organ of body, containing neurons several types glial cells different origins properties that protect ensure normal structure function. Neurological disorders are result a failure nervous system multifaceted cellular networks. Although great progress has been made in understanding glia involvement neuropathology, therapeutic outcomes still not satisfactory. Here, we discuss recent perspectives on role microglia astrocytes neurological disorders, including two common neurodegenerative conditions, Alzheimer disease progranulin-related frontotemporal lobar dementia, as well astrocytoma tumors. We emphasize key factors astrocytic biology such highly heterogeneic nature strongly dependent environment, genetic predispose to certain pathologies senescence inevitably changes CNS landscape. Our diverse contributions diseases can lead advances their functional recovery after malfunction.

Язык: Английский

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