Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Май 11, 2023

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up 27% patients with MDD associated more severe, chronic, treatment-resistant trajectory. Inflammation not unique depression has transdiagnostic effects suggesting shared underlying psychopathologies metabolic disorders. Research supports association but necessarily causation Putative mechanisms link dysregulation the HPA axis immune cell glucocorticoid resistance resulting in hyperactivation peripheral system. The extracellular release DAMPs DAMP-PRR signaling creates feed forward loop that accelerates central inflammation. Higher plasma levels inflammatory cytokines, most consistently interleukin IL-1β, IL-6, TNF-α, are correlated greater depressive symptomatology. Cytokines sensitize axis, disrupt negative feedback loop, further propagate reactions. Peripheral inflammation exacerbates (neuroinflammation) through several including disruption blood-brain barrier, cellular trafficking, activation glial cells. Activated cells chemokines, reactive oxygen nitrogen species into extra-synaptic space dysregulating neurotransmitter systems, imbalancing excitatory inhibitory ratio, disrupting neural circuitry plasticity adaptation. particular, microglial toxicity plays role pathophysiology neuroinflammation. Magnetic resonance imaging (MRI) studies show reduced hippocampal volumes. Neural dysfunction such as hypoactivation between ventral striatum ventromedial prefrontal cortex underlies melancholic phenotype Chronic administration monoamine-based antidepressants counters response, delayed therapeutic onset. Therapeutics targeting mediated immunity, generalized specific pathways, nitro-oxidative have enormous potential advance treatment landscape. Future clinical trials will need include system perturbations biomarker outcome measures facilitate novel antidepressant development. this overview, we explore correlates elucidate pathomechanisms development biomarkers therapeutics.

Язык: Английский

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The chronic unpredictable mild stress (CUMS) Paradigm: Bridging the gap in depression research from bench to bedside

Brain Research, Год журнала: 2024, Номер 1843, С. 149123 - 149123

Опубликована: Ноя. 1, 2024

Язык: Английский

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Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(6), С. 1727 - 1727

Опубликована: Март 17, 2024

Major Depressive Disorder (MDD) is one of the most disabling diseases in world. MDD traditionally diagnosed based on a patient’s symptoms, which can lead to misdiagnosis. Although pathogenic mechanisms are unknown, several studies have identified mitochondrial dysfunction as central factor onset and progression MDD. In context MDD, alterations metabolism imbalances energy production oxidative stress, contributing disorder´s underlying pathophysiological mechanisms. Consequently, identification key biomarker for early accurate diagnosis represents significant challenge. Faced with limits traditional treatments antidepressants, new pharmacological therapeutic targets being investigated such ketamine/esketamine, psychedelics, or anti-inflammatories. All these drugs show potential antidepressant effects due their speed action ability modulate neuroplasticity and/or motor processing. parallel, non-pharmacological studied, like Transcranial Magnetic Stimulation (TMS) Deep Brain (DBS), recognized neuronal activity offer treatment alternatives. As cellular directly related respiration, aim this review examining link between assessing how biomarkers could provide more objective precise diagnostic tool, exploring other addition specific focus emerging targets. Finally, detailed analysis strengths, weaknesses, opportunities, threats approaches was carried out, highlighting challenges that must be addressed.

Язык: Английский

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Neuroinflammation—A Crucial Factor in the Pathophysiology of Depression—A Comprehensive Review

Biomolecules, Год журнала: 2025, Номер 15(4), С. 502 - 502

Опубликована: Март 30, 2025

Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood-brain barrier dysfunction, and disruptions neurotransmitter systems. article highlights how inflammatory mediators influence brain regions implicated mood regulation, such as hippocampus, amygdala, prefrontal cortex. further discusses involvement hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, kynurenine pathway, providing mechanistic insights into chronic inflammation may underlie emotional cognitive symptoms depression. bidirectional relationship between depressive emphasized, along peripheral immune responses systemic stress. By integrating molecular, cellular, neuroendocrine perspectives, this supports growing field immunopsychiatry lays foundation for novel diagnostic biomarkers anti-inflammatory treatment approaches Further research holds promise developing more effective personalized interventions individuals suffering from

Язык: Английский

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Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 6888 - 6888

Опубликована: Апрель 7, 2023

Major depressive disorder is one of the most common mental illnesses that highly impairs quality life. Pharmacological interventions are mainly focused on altered monoamine neurotransmission, which considered primary event underlying disease's etiology. However, many other neuropathological mechanisms contribute to progression and clinical symptoms have been identified. These include oxidative stress, neuroinflammation, hippocampal atrophy, reduced synaptic plasticity neurogenesis, depletion neurotrophic factors, dysfunction hypothalamic-pituitary-adrenal (HPA) axis. Current therapeutic options often unsatisfactory associated with adverse effects. This review highlights relevant findings concerning role flavonols, a ubiquitous class flavonoids in human diet, as potential antidepressant agents. In general, flavonols be both an effective safe option management depression, largely based their prominent antioxidative anti-inflammatory Moreover, preclinical studies provided evidence they capable restoring neuroendocrine control HPA axis, promoting alleviating depressive-like behavior. Although these promising, still far from being implemented practice. Hence, further needed more comprehensively evaluate respect improvement signs depression.

Язык: Английский

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Role of brain renin–angiotensin system in depression: A new perspective

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(4)

Опубликована: Ноя. 12, 2023

Abstract Depression is a mood disorder characterized by abnormal thoughts. The pathophysiology of depression related to the deficiency serotonin (5HT), which derived from tryptophan (Trp). Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in pathogenesis depression. Notably, renin–angiotensin system (RAS) depression, different findings revealed that angiotensin‐converting enzyme inhibitors (ACEIs) angiotensin receptor blockers (ARBs) may be effective However, underlying mechanism for role dysregulated brain RAS‐induced remains speculative. Therefore, this review aimed revise conceivable ACEIs ARBs how these agents ameliorate Dysregulation RAS triggers development progression through reduction 5HT expression brain‐derived neurotrophic factor (BDNF) induction mitochondrial neuroinflammation. inhibition central classical ARBS activation non‐classical prevent regulating 5HT, BDNF,

Язык: Английский

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Kaempferol Improves Breast Cancer-Related Depression through the COX-2/PGE2 Pathway

Frontiers in Bioscience-Landmark, Год журнала: 2023, Номер 28(11), С. 311 - 311

Опубликована: Ноя. 28, 2023

Background: Breast cancer-related depression (BCRD) is strongly associated with BC and increases recurrence mortality. This study investigated the role of kaempferol in pathogenesis BCRD its underlying mechanism. Methods: 4T1 mouse cells were treated corticosterone (Cort) vitro to develop a neuronal injury model, model was established by injecting Cort. The effects on models measured behavioral tests, Cell Counting Kit-8 assay, wound healing colony formation Western blot analysis, quantitative real-time PCR, hematoxylin eosin staining, enzyme-linked immunosorbent immunofluorescence. transfected cyclo-oxygenase-2 (COX-2) overexpression plasmid COX-2/prostaglandin E2 (PGE2) axis anti-BCRD activity kaempferol. connection between COX-2 analyzed molecular docking. Results: Kaempferol reduced viability, migration, clones inhibited growth depression-like behavior mice. alleviated inflammation BCRD, decreased interleukin 1 beta (IL-1β) IL-6 levels, increased transforming factor (TGF-β1) IL-10 levels. In addition, elevated levels serotonin, dopamine, norepinephrine amount 5-Bromo-2′-deoxyuridine/neuronal nuclei-positive cells. downregulated PGE2, could dock protein structure COX-2. Overexpression upregulated IL-1β TGF-β1 expression. reversed protective Conclusion: exerted effects, at least part inhibiting COX-2/PGE2 pathway, which regulates neuroinflammation, neurotransmitter imbalance, defective neurogenesis. Therefore, may be promising candidate active ingredient for treating BCRD.

Язык: Английский

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Deciphering the mechanisms of reciprocal regulation or interdependence at the cannabinoid CB1 receptors and cyclooxygenase-2 level: Effects on mood, cognitive implications, and synaptic signaling

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 155, С. 105439 - 105439

Опубликована: Окт. 27, 2023

Язык: Английский

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Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments

Nutrients, Год журнала: 2024, Номер 16(8), С. 1167 - 1167

Опубликована: Апрель 14, 2024

Polygonati Rhizoma (PR) has certain neuroprotective effects as a homology of medicine and food. In this study, systematic pharmacology, molecular docking, in vitro experiments were integrated to verify the antidepressant active ingredients PR their mechanisms. A total seven compounds found be associated with 45 targets depression. Preliminarily, DFV docking cyclooxygenase 2 (COX2) showed good affinity. vitro, inhibited lipopolysaccharide (LPS)-induced inflammation BV-2 cells, reversed amoeba-like morphological changes, increased mitochondrial membrane potential. malondialdehyde (MDA) overexpression superoxide dismutase (SOD) expression inhibition LPS-induced cells decreased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 mRNA levels dose-dependent manner. both protein COX2 induced by LPS, activation NACHT, LRR, PYD domains-containing 3 (NLRP3) caspase1 was suppressed, thus exerting an effect. This study proves that may important component basis for play role.

Язык: Английский

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Bambusa vulgaris Extract: A Potential Natural Biogenic Amine Neurotransmitters Modulator, COX-2 Inhibitor and Oxidative Species Suppressor for Managing Depression and Anxiety

Natural Product Communications, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 1, 2025

Objective Literature reveals a significant deficiency in scientific investigations regarding the use of Bambusa vulgaris extract (BVE) for treatment neuropsychiatric disorders, particularly those characterized by anxiety and depression. Thus, this study was designed to examine anxiolytic antidepressant-like properties BVE using mouse models, while also elucidating potential underlying mechanisms responsible observed antidepressant effects extract. Methods Validated behavioral assessments were employed assess (including hole-board test (HBT), open field (OFT), elevated plus maze (EPMT), light/dark exploration (LDET)) as well (comprising forced swim (FST) tail suspension (TST)) Chronic mild stress paradigms induce depressive-like behaviors subjects. The mice administered treatments consisting distilled water (10 mL/kg; serving negative control), fluoxetine (20 mg/kg; standard drug), (at varying doses 100, 200, 400 mg/kg). concentrations biogenic amine neurotransmitters (noradrenaline serotonin) cyclooxygenase-2 (COX-2) within brain measured ELISA kits. Antioxidant biomarkers assessed through application standardized commercial assay Results significantly diminished levels subjects, demonstrated an enhancement exploratory activities light/open enclosures increased aversion darker compartments. Furthermore, alleviated depression-like mice, which reflected latency immobility reduction overall duration immobility. enhanced noradrenaline serotonin neurotransmission, suppressed oxidative species, inhibited COX-2 activity. Conclusion results obtained from suggest that demonstrates properties, latter being mediated serotonin), inhibition activity, suppression radicals brain.

Язык: Английский

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