Microbiota–gut–brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(7), P. 2645 - 2673

Published: Jan. 27, 2023

Abstract Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is complex picture genetic environmental factors implicated. Nowadays, gut microbiota in spotlight new research related to this kind psychiatric disorder, as can be consistently several pathophysiological events observed BD. In context so-called microbiota–gut–brain (MGB) axis, shown have strong influence on host neuromodulation endocrine functions (i.e., controlling synthesis neurotransmitters like serotonin or mediating activation hypothalamic–pituitary–adrenal axis), well modulation immune responses, critically regulating intestinal, systemic brain inflammation (neuroinflammation). present review aims elucidate derived from MGB axis disruption possible therapeutic approaches mainly focusing network Understanding its bidirectional communication other systems shed light discovery therapies for improving clinical management these patients. Besides, effect drugs currently used patients, together therapeutical targeting ecosystem (dietary patterns, probiotics, prebiotics, novelties) will also contemplated.

Language: Английский

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Targeting inflammation: a potential approach for the treatment of depression

Metabolic Brain Disease, Journal Year: 2022, Volume and Issue: 38(1), P. 45 - 59

Published: Oct. 14, 2022

Language: Английский

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Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(3), P. 825 - 875

Published: June 23, 2022

Carbon monoxide (CO) has been firmly established as an endogenous signaling molecule with a variety of pathophysiological and pharmacological functions, including immunomodulation, organ protection, circadian clock regulation, among many others. In terms its molecular mechanism(s) action, CO is known to bind large number hemoproteins at least 25 identified targets, hemoglobin, myoglobin, neuroglobin, cytochrome c oxidase, P450, soluble guanylyl cyclase, myeloperoxidase, some ion channels dissociation constant values spanning the range sub-nM high μM. Although CO's binding affinity targets extensively studied established, there pressing need incorporate such information into analysis biologic response in context dosage. Especially important understand reservoir role hemoglobin storage, transport, distribution, transfer. We critically review literature inject sense quantitative assessment our analyses various relationships affinity, concentration, target occupancy level, anticipated actions. hope that this presents picture overall landscape engagement stimulates additional research, helps move field direction examining individual all concentration available CO. believe work will help further understanding relationship functions eventual development CO-based therapeutics.

Significance Statement

The carbon therapeutic agent significantly rely on therapeutically relevant varying affinity. This examines by quantitatively analyzing intricate for CO, state carboxyhemoglobin provide holistic approach action

Language: Английский

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A multiscale inflammatory map: linking individual stress to societal dysfunction

Frontiers in Science, Journal Year: 2024, Volume and Issue: 1

Published: March 12, 2024

As populations worldwide show increasing levels of stress, understanding emerging links among inflammation, cognition, and behavior is vital to human planetary health. We hypothesize that inflammation a multiscale driver connecting stressors affect individuals large-scale societal dysfunction and, ultimately, planetary-scale environmental impacts. propose “central map” hypothesis explain how the brain regulates impairs emotion, action. According our hypothesis, these interdependent inflammatory neural processes, inter-individual transmission environmental, infectious, behavioral stressors—amplified via high-throughput digital global communications—can culminate in multiscale, runaway, feed-forward process could detrimentally decision-making at scale, ultimately impairing ability address same stressors. This perspective provide non-intuitive explanations for behaviors relationships cells, organisms, communities potentially including population-level responses as diverse climate change, conflicts, COVID-19 pandemic. To illustrate elucidate its mechanistic underpinnings, we present mathematical model applicable individual test control, healing, implications transmission, intervention (e.g., lifestyle modification or medication), resilience. Future research needed validate model’s assumptions conclusions against empirical benchmarks expand factors/variables employed. Our illustrates need multilayered, stress mitigation interventions, measures, precision therapeutics, ecosystem design. analysis shows coordinated, interdisciplinary, international effort understand nature stress. Doing so would inform creation interventions improve individuals’ lives; enhance communities’ resilience stress; mitigate adverse effects on world.

Language: Английский

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Inflammaging and Brain Aging

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

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Circadian clock gene polymorphisms implicated in human pathologies

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(10), P. 834 - 852

Published: June 12, 2024

Circadian rhythms, ~24 h cycles of physiological and behavioral processes, can be synchronized by external signals (e.g., light) persist even in their absence. Consequently, dysregulation circadian rhythms adversely affects the well-being organism. This timekeeping system is generated sustained a genetically encoded endogenous mechanism composed interlocking transcriptional/translational feedback loops that generate rhythmic expression core clock genes. Genome-wide association studies (GWAS) forward genetic show SNPs genes influence gene regulation correlate with risk developing various conditions. We discuss variations are associated phenotypes, implications for human health, stress need thorough this domain regulation.

Language: Английский

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Integrated multi-omics analysis reveals the molecular interplay between circadian clocks and cancer pathogenesis

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 30, 2023

Circadian rhythms (CRs) are fundamental biological processes that significantly impact human well-being. Disruption of these can trigger insufficient neurocognitive development, insomnia, mental disorders, cardiovascular diseases, metabolic dysfunctions, and cancer. The field chronobiology has increased our understanding how rhythm disturbances contribute to cancer pathogenesis, circadian timing influences the efficacy treatments. As clock steadily gains recognition as an emerging factor in tumorigenesis, a thorough comprehensive multi-omics analysis CR genes/proteins never been performed. To shed light on this, we performed, for first time, integrated data encompassing genomic/transcriptomic alterations across 32 types (n = 10,918 tumors) taken from PanCancer Atlas, unfavorable prognostic protein analysis, protein-protein interactomics, shortest distance score pathways hallmark phenotypes. This mining strategy allowed us unravel 31 essential CR-related proteins involved signaling crossroad between In context drugging clock, identified pharmacogenomic clinical annotations drugs currently late phase trials could be considered potential therapeutic strategies. These findings highlight diverse roles realm research therapy.

Language: Английский

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Aryl hydrocarbon receptor (AhR) impairs circadian regulation: Impact on the aging process

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101928 - 101928

Published: April 7, 2023

Circadian clocks control the internal sleep-wake rhythmicity of 24 h which is synchronized by solar cycle. regulation metabolism evolved about 2.5 billion years ago, i.e., has been conserved from cyanobacteria and Archaea through to mammals although mechanisms utilized have developed with evolution. While aryl hydrocarbon receptor (AhR) an evolutionarily defence mechanism against environmental threats, it gained many novel functions during evolution, such as cell cycle, proteostasis, immune functions. There robust evidence that AhR signaling impairs circadian rhythmicity, e.g., interacting core BMAL1/CLOCK complex disturbing epigenetic clock genes. The maintenance rhythms impaired aging, important in aged organisms. Interestingly, known promotes age-related tissue degeneration, able inhibit autophagy, enhance cellular senescence, disrupt extracellular matrix. These alterations are rather similar those induced a long-term impairment rhythms. However, not whether enhances aging process impairing homeostasis. I will examine experimental indicating promote degeneration via disruption rhythmicity.

Language: Английский

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Relationship between the Biological Clock and Inflammatory Bowel Disease

Clocks & Sleep, Journal Year: 2023, Volume and Issue: 5(2), P. 260 - 275

Published: May 12, 2023

The biological clock is a molecular oscillator that generates 24-hour rhythm in accordance with the earth’s rotation. Physiological functions and pathophysiological processes such as inflammatory bowel diseases (IBD) are closely linked to clock. This review summarizes 14 studies humans mice on interactions between IBD. It provides evidence IBD negatively affect core gene expression, metabolism immune functions. On other hand, disruption of promotes inflammation. Overexpression genes can lead inhibition processes, while silencing irreversible disease activity. In both human mouse studies, circadian rhythms have been shown influence each other. Further research needed understand exact mechanisms develop potential rhythm-related therapies improve

Language: Английский

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Chronic Inflammation Disrupts Circadian Rhythms in Splenic CD4+ and CD8+ T Cells in Mice

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 151 - 151

Published: Jan. 13, 2024

Internal circadian clocks coordinate 24 h rhythms in behavior and physiology. Many immune functions show daily oscillations, cellular can impact disease outcome. Inflammation may disrupt peripheral tissues innate cells. However, it remains elusive if chronic inflammation impacts adaptive cell clock, e.g., CD4+ CD8+ T lymphocytes. We studied this the experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis, as an established paradigm inflammation. analyzed splenic clock gene expression mice with late-stage EAE, CFA/PTx-treated, untreated mice. In both treatment groups, were altered differential effects baseline peak phase compared control Most marker genes tested study did not oscillations either of three but time-of-day- independent alterations observed EAE CFA/PTx to Notably, likely central function behavioral remained intact. Together, induced by immunization has lasting on

Language: Английский

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