Primary microglia cell cultures in translational research: Strengths and limitations

Journal of Biotechnology, Год журнала: 2024, Номер 386, С. 10 - 18

Опубликована: Март 20, 2024

Microglia are the resident macrophages in central nervous system, accounting for 10-15% of cell mass brain. Next to their physiological role development, monitoring neuronal function and maintenance homeostasis, microglia crucial brain's immune defense. Brain injury chronic neurological disorders associated with neuroinflammation, which activation is a element. acquire wide spectrum states diseased or injured brain, some neurotoxic. The investigation (patho)physiology therapeutic interventions targeting neuroinflammation substantial challenge. In addition vivo approaches, application vitro model systems has gained significant ground essential complement work. Primary cultures have proved be useful tool. offered opportunity explore mechanistic, molecular elements activation, secretome, efficacy treatments against neuroinflammation. As all systems, primary distinct strengths limitations weighed when experiments designed data interpreted. Here, we set out provide succinct overview advantages pitfalls use cultures, instructs refinement further development this technique remain toolbox researchers. Since there no conclusive therapy combat neurotoxicity linked acute brain neurodegenerative disorders, these research tools opportunities.

Язык: Английский

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Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis

MedComm, Год журнала: 2024, Номер 5(4)

Опубликована: Апрель 1, 2024

Abstract Autoimmune uveitis (AU) is a kind of immune‐mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to initiation progression AU remains unclear. Here, we induced an experimental (EAU) model with IRBP 651‐670 found that day[D]14 was inflammatory summit remarking clinical histopathological manifestations activation retinal microglia exhibited time‐dependent pattern EAU course. We conducted single‐cell RNA sequencing cells mice at four time points constituting largest proportion, especially on D14. A novel subtype ( Cd74 high Ccl5 ) identified peak closely associated modulating responses. In vitro experiments indicated stimuli proinflammatory upregulation CD74 CCL5, overexpression elicited their phenotype via nuclear factor‐kappa B signaling could be attenuated by treatment neutralizing CCL5 antibody certain extent. In‐vivo blockade effectively alleviated microglial EAU. Therefore, propose targeting as promising strategies for treatment.

Язык: Английский

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Tracking inflammation status for improving patient prognosis: A review of current methods, unmet clinical needs and opportunities

Biotechnology Advances, Год журнала: 2025, Номер unknown, С. 108592 - 108592

Опубликована: Май 1, 2025

Язык: Английский

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Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations

Journal of Neurochemistry, Год журнала: 2023, Номер 168(5), С. 608 - 631

Опубликована: Июнь 13, 2023

Abstract Lactate shuttled from the blood circulation, astrocytes, oligodendrocytes or even activated microglia (resident macrophages) to neurons has been hypothesized represent a major source of pyruvate compared what is normally produced endogenously by neuronal glucose metabolism. However, role lactate oxidation in fueling signaling associated with complex cortex function, such as perception, motor activity, and memory formation, widely unclear. This issue experimentally addressed using electrophysiology hippocampal slice preparations (ex vivo) that permit induction different neural network activation states electrical stimulation, optogenetic tools receptor ligand application. Collectively, these studies suggest absence (lactate only) impairs gamma (30–70 Hz) theta‐gamma oscillations, which feature high energy demand revealed cerebral metabolic rate oxygen (CMRO2, set 100%). The impairment comprises oscillation attenuation moderate bursts (excitation–inhibition imbalance). bursting suppressed elevating fraction substrate supply. By contrast, can retain certain electric stimulus‐induced population responses intermittent sharp wave‐ripple activity features lower expenditure (CMRO2 about 65%). utilization increases consumption 9% during wave‐ripples reflecting enhanced adenosine‐5′‐triphosphate (ATP) synthesis oxidative phosphorylation mitochondria. Moreover, attenuates neurotransmission glutamatergic pyramidal cells fast‐spiking, γ‐aminobutyric acid (GABA)ergic interneurons reducing neurotransmitter release presynaptic terminals. generation propagation action potentials axon regular. In conclusion, less effective than potentially detrimental rhythms featuring energetic costs, likely through lack some obligatory ATP aerobic glycolysis at excitatory inhibitory synapses. High lactate/glucose ratios might contribute central fatigue, cognitive impairment, epileptic seizures partially seen, for instance, exhaustive physical exercise, hypoglycemia neuroinflammation. image

Язык: Английский

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Ketogenic diet changes microglial morphology and the hippocampal lipidomic profile differently in stress susceptible versus resistant male mice upon repeated social defeat

Brain Behavior and Immunity, Год журнала: 2023, Номер 114, С. 383 - 406

Опубликована: Сен. 7, 2023

Язык: Английский

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Moderate intrinsic phenotypic alterations in C9orf72 ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июнь 6, 2023

While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis frontotemporal dementia (ALS/FTD), it remains largely unknown if how non-neuronal cells induce or exacerbate neuronal damage. We differentiated ALS/FTD patient-derived induced pluripotent stem into microglia (iPSC-MG) examined their intrinsic phenotypes. Similar to iPSC neurons, iPSC-MG mono-cultures form G 4 C 2 repeat RNA foci, exhibit reduced protein levels, generate dipeptide proteins. Healthy control equally express microglial specific genes perform functions, including inflammatory cytokine release phagocytosis of extracellular cargos, such as synthetic amyloid beta peptides healthy human brain synaptoneurosomes. sequencing analysis revealed select transcriptional changes associated with neuroinflammation neurodegeneration diseased yet no significant differentially expressed microglial-enriched genes. Moderate molecular functional differences were observed despite the presence pathological features suggesting that a microenvironment may be required phenotypic dysfunction seen neurodegeneration.

Язык: Английский

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Management of the Brain: Essential Oils as Promising Neuroinflammation Modulator in Neurodegenerative Diseases

Antioxidants, Год журнала: 2024, Номер 13(2), С. 178 - 178

Опубликована: Янв. 31, 2024

Neuroinflammation, a pivotal factor in the pathogenesis of various brain disorders, including neurodegenerative diseases, has become focal point for therapeutic exploration. This review highlights neuroinflammatory mechanisms that hallmark diseases and potential benefits essential oils counteracting neuroinflammation oxidative stress, thereby offering novel strategy managing mitigating impact disorders. Essential oils, derived from aromatic plants, have emerged as versatile compounds with myriad health benefits. exhibit robust antioxidant activity, serving scavengers free radicals contributing to cellular defense against stress. Furthermore, showcase anti-inflammatory properties, modulating immune responses inflammatory processes implicated chronic diseases. The intricate by which phytomolecules exert their effects were explored, shedding light on multifaceted properties. Notably, we discussed ability modulate diverse pathways crucial maintaining homeostasis suppressing responses, capacity rescue cognitive deficits observed preclinical models neurotoxicity

Язык: Английский

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Microglial priming by IFN‐γ involves STAT1‐mediated activation of the NLRP3 inflammasome

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)

Опубликована: Окт. 1, 2024

Abstract Background Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial “priming”. Interferon (IFN)‐γ is known cause priming, but mechanism unclear. Methods We examined effects of IFN‐γ on gene expression, activation, inflammatory activity NLRP3 inflammasome primary microglia brains mice. Results Our results showed treating cultures with induced a hedgehog‐like morphology upregulated markers activation (CD86, CD11b) pro‐inflammatory molecules (IL‐1β, IL‐6, TNF‐α, iNOS), while downregulating homeostasis (CX3CR1, CD200R1), anti‐inflammatory (MCR1, Arg‐1) neurotrophic factors (IGF‐1, BDNF). also (NLRP3, caspase‐1, gasdermin D, IL‐18). This particular transcriptional profiling makes IFN‐γ‐primed exaggerated upon lipopolysaccharide (LPS) stimulation. The level NLRP3, IL‐1β, IL‐18, TNF‐α iNOS treated both LPS were highest than either one alone. Injecting into lateral ventricle mice similar morphological functional changes hippocampal cultures. from or hippocampus abolished when STAT1 was inhibited using fludarabin. alone together anxiety‐ depression‐like behaviors impaired hippocampus‐dependent spatial memory; these mitigated by Conclusions primes activating STAT1, which upregulates genes activate inflammasome. Inhibiting IFN‐γ/STAT1 axis be way treat neurodegenerative diseases psychiatric involve priming.

Язык: Английский

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High throughput screening identifies auranofin and pentamidine as potent compounds that lower IFN-γ-induced Nitric Oxide and inflammatory responses in mice: DSS-induced colitis and Salmonella Typhimurium-induced sepsis

International Immunopharmacology, Год журнала: 2023, Номер 122, С. 110569 - 110569

Опубликована: Июнь 29, 2023

Язык: Английский

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High-throughput CRISPR technology: a novel horizon for solid organ transplantation

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Organ transplantation is the gold standard therapy for end-stage organ failure. However, shortage of available grafts and long-term graft dysfunction remain primary barriers to transplantation. Exploring approaches solve these issues urgent, CRISPR/Cas9-based transcriptome editing provides one potential solution. Furthermore, combining gene with an ex vivo perfusion system would enable pre-implantation grafts. How determine effective intervention targets becomes a new problem. Fortunately, advent high-throughput CRISPR screening has dramatically accelerated targets. This review summarizes current advancements, utilization, workflow in various immune non-immune cells. It also discusses ongoing applications CRISPR/Cas-based prospective solid

Язык: Английский

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