Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications

General Psychiatry, Journal Year: 2024, Volume and Issue: 37(1), P. e101374 - e101374

Published: Feb. 1, 2024

The gut microbiota is a complex and dynamic ecosystem known as the ‘second brain’. Composing microbiota-gut-brain axis, its metabolites regulate central nervous system through neural, endocrine immune pathways to ensure normal functioning of organism, tuning individuals’ health disease status. Short-chain fatty acids (SCFAs), main bioactive microbiota, are involved in several neuropsychiatric disorders, including depression. SCFAs have essential effects on each component axis In present review, roles major (acetate, propionate butyrate) pathophysiology depression summarised with respect chronic cerebral hypoperfusion, neuroinflammation, host epigenome neuroendocrine alterations. Concluding remarks biological mechanisms related will hopefully address clinical value microbiota-related treatments for

Language: Английский

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Brain energy metabolism: A roadmap for future research

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 168(5), P. 910 - 954

Published: Jan. 6, 2024

Although we have learned much about how the brain fuels its functions over last decades, there remains still to discover in an organ that is so complex. This article lays out major gaps our knowledge of interrelationships between metabolism and function, including biochemical, cellular, subcellular aspects functional imaging adult brain, as well during development, aging, disease. The focus on unknowns substrates associated transporters, roles insulin lipid droplets, emerging role microglia, mysteries cofactor signaling molecule NAD

Language: Английский

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Neuroinflammation in Alzheimer disease

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Language: Английский

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Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 21, 2025

Abstract Alzheimer’s disease (AD) poses a growing global health challenge as populations age. Recent research highlights the crucial role of peripheral immunity in AD pathogenesis. This review explores how blood-brain barrier disruption allows immune cells to infiltrate central nervous system (CNS), worsening neuroinflammation and progression. We examine recent findings on interactions between CNS-resident microglia, forming self-perpetuating inflammatory cycle leading neuronal dysfunction. Moreover, this emphasizes developments dysregulation factors from both periphery CNS, their impact With ongoing development new therapeutic strategies, underscores importance modulating CNS therapy.

Language: Английский

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Microglial Activation and Priming in Alzheimer’s Disease: State of the Art and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 884 - 884

Published: Jan. 3, 2023

Alzheimer’s Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) protein Tau aggregates are disease hallmarks key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to pathophysiology, as well. Microglia CNS-resident immune cells belonging myeloid lineage innate arm immunity. Under physiological conditions, constant motion order carry on their housekeeping function, they maintain an anti-inflammatory, quiescent state, with low expression cytokines no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, pathogens), acquire function overexpress cytokine gene modules. This process generally regarded activation implies production pro-inflammatory counterbalanced by synthesis release anti-inflammatory molecules. mechanism avoids excessive inflammatory response inappropriate microglial activation, which causes tissue damage brain homeostasis impairment. Once pathogenic stimulus cleared, activated return naïve, state. repeated (as case Aβ deposition early stage AD), shift toward less protective, neurotoxic phenotype, known “primed” microglia. The main characteristic primed lower capability turn back makes these prone chronic favours inflammation brain. Primed have impaired defence capacity against injury detrimental effects microenvironment. Additionally, priming associated onset progression represent promising target for treatment strategies. Many factors (genetics, environmental factors, baseline status microglia, ageing) generate aberrantly phenotype undergoes easier earlier than normally do. Novel, targets therapeutic strategies sought field and, importantly, among those influencing cells. CX3CL1 pathway could be valuable approach AD, although preliminary findings from studies this controversial. current review aims summarize state art role dysfunction pathogenesis proposes biochemical pathways possible treatment.

Language: Английский

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Redox Pathogenesis in Rheumatic Diseases

ACR Open Rheumatology, Journal Year: 2024, Volume and Issue: 6(6), P. 334 - 346

Published: April 25, 2024

Despite being some of the most anecdotally well-known roads to pathogenesis, mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation cellular immune system and characteristic development autoantibodies have been linked oxidative stress. Typical clinical manifestations, such as joint swelling deformities inflammation skin internal organs, also connected directly or indirectly redox mechanisms. differences in generation restraint stress provide compelling evidence for broad variety pathology among explain common triggers discordant manifestations these diseases. Growing pathogenesis has provided a array new potential therapeutic targets. Here, we explore by which is generated, its roles autoimmunity end-organ damage, discuss how individual exhibit unique features that offer targets interventions.

Language: Английский

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Metabolic flexibility ensures proper neuronal network function in moderate neuroinflammation

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

Published: June 22, 2024

Abstract Microglia, brain-resident macrophages, can acquire distinct functional phenotypes, which are supported by differential reprogramming of cell metabolism. These adaptations include remodeling in glycolytic and mitochondrial metabolic fluxes, potentially altering energy substrate availability at the tissue level. This phenomenon may be highly relevant brain, where metabolism must precisely regulated to maintain appropriate neuronal excitability synaptic transmission. Direct evidence that microglia impact on has been widely lacking, however. Combining molecular profiling, electrophysiology, oxygen microsensor recordings mathematical modeling, we investigated microglia-mediated disturbances brain energetics during neuroinflammation. Our results suggest proinflammatory showing enhanced nitric oxide release decreased CX3CR1 expression transiently increase lactate/glucose ratio depends transcriptional microglia, not neurons. In this condition, network activity such as gamma oscillations (30–70 Hz) fueled increased ATP production mitochondria, is reflected elevated consumption. During dysregulated inflammation, high demand low glucose boundary conditions for fitness revealed kinetic modeling single neuron energetics. Collectively, these findings indicate flexibility protects function against alterations local moderate

Language: Английский

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The Functions and Phenotypes of Microglia in Alzheimer’s Disease

Cells, Journal Year: 2023, Volume and Issue: 12(8), P. 1207 - 1207

Published: April 21, 2023

Alzheimer’s disease (AD) is the most prevalent neurodegenerative worldwide, but therapeutic strategies to slow down AD pathology and symptoms have not yet been successful. While attention has focused on neurodegeneration in pathogenesis, recent decades provided evidence of importance microglia, resident immune cells central nervous system. In addition, new technologies, including single-cell RNA sequencing, revealed heterogeneous cell states microglia AD. this review, we systematically summarize microglial response amyloid-β tau tangles, risk factor genes expressed microglia. Furthermore, discuss characteristics protective that appear during relationship between microglia-induced inflammation chronic pain. Understanding diverse roles will help identify for

Language: Английский

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Edaravone dexborneol promotes M2 microglia polarization against lipopolysaccharide-induced inflammation via suppressing TLR4/MyD88/NF-κB pathway

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(9), P. 6647 - 6659

Published: March 15, 2024

Language: Английский

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Primary microglia cell cultures in translational research: Strengths and limitations

Journal of Biotechnology, Journal Year: 2024, Volume and Issue: 386, P. 10 - 18

Published: March 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.

Language: Английский

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