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

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: May 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.

Language: Английский

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The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 19, 2025

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to disorders. This review elucidates the complex interplay between peripheral and central components underlying pathology. Peripherally, systemic inflammation, gut dysregulation, dysfunction in organs including gut, liver, spleen adipose tissue influence brain function through neural molecular pathways. Within nervous system, aberrant microglial astrocytes activation, cytokine imbalances, compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, promoting neuronal injury. The crosstalk immunity creates vicious cycle exacerbating neuropathology. Unraveling these multifaceted immune-mediated provides insights into major disorder's pathogenic basis potential biomarkers targets. Modulating both responses represent promising multidimensional therapeutic strategy.

Language: Английский

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Critical Review of the Cross-Links Between Dietary Components, the Gut Microbiome, and Depression

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 614 - 614

Published: Jan. 13, 2025

The complex relationship between diet, the gut microbiota, and mental health, particularly depression, has become a focal point of contemporary research. This critical review examines how specific dietary components, such as fiber, proteins, fats, vitamins, minerals, bioactive compounds, shape microbiome influence microbial metabolism in order to regulate depressive outcomes. These dietary-induced changes microbiota can modulate production metabolites, which play vital roles gut–brain communication. axis facilitates this communication through neural, immune, endocrine pathways. Alterations metabolites central nervous system (CNS) functions by impacting neuroplasticity, inflammatory responses, neurotransmitter levels—all are linked onset course depression. highlights recent findings linking components with beneficial composition reduced symptoms. We also explore challenges individual variability responses interventions long-term sustainability these strategies. underscores necessity for further longitudinal mechanistic studies elucidate precise mechanisms diet interactions be leveraged mitigate paving way personalized nutritional therapies.

Language: Английский

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Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 115 - 115

Published: Jan. 7, 2025

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery quality of life. As the aging population grows, rising number patients has made PND an urgent clinical challenge. Despite increasing research efforts, pathophysiological mechanisms underlying remain inadequately characterized, underscoring need for more integrated framework to guide targeted interventions. To better understand molecular therapeutic targets PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches PubMed, Embase, Cochrane Library, Web Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, white matter lesions as central pathophysiology, with particular parallels encephalocele- sepsis-associated impairments. Among these, mediated pathways such NLRP3 inflammasome blood-brain barrier disruption, emerges pivotal driver, triggering cascades exacerbate neuronal injury. Oxidative stress synergistically amplify these effects, while imbalances alterations, including lesions, contribute synaptic decline. Anesthetic agents modulate interconnected pathways, exhibiting both protective detrimental effects. Propofol dexmedetomidine demonstrate neuroprotective properties suppressing neuroinflammation microglial activation, whereas inhalational anesthetics like sevoflurane intensify inflammatory responses. Ketamine, its anti-inflammatory potential, offers promise but requires further evaluation determine long-term safety efficacy. By bridging insights practice, highlights critical role personalized anesthetic strategies mitigating improving patients. It aims inform future decision-making address multifaceted

Language: Английский

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Astrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 7, 2023

Abstract Astrocytes contribute to brain inflammation in neurological disorders but the molecular mechanisms controlling astrocyte reactivity and their relationship neuroinflammatory endpoints are complex poorly understood. In this study, we assessed role of calcium channel, Orai1, for inflammation-evoked depression behaviors mice. Transcriptomics metabolomics analysis indicated that deletion Orai1 astrocytes downregulates genes immunity, metabolism, cell cycle pathways, reduces cellular metabolites ATP production. Systemic by peripheral lipopolysaccharide (LPS) increases hippocampal inflammatory markers WT not knockout Loss also blunts inflammation-induced Ca 2+ signaling inhibitory neurotransmission hippocampus. line with these changes, mice showed amelioration LPS-evoked depression-like including anhedonia helplessness. These findings identify as an important hub astrocyte-mediated is commonly observed many disorders.

Language: Английский

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Interplay between stress and cancer—A focus on inflammation

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: March 20, 2023

Stress is an integral part of life. While acute responses to stress are generally regarded as beneficial in dealing with immediate threats, chronic exposure threatening stimuli exerts deleterious effects and can be either a contributing or aggravating factor for many diseases including cancer. Chronic psychological has been identified significant the development progression cancer, but mechanisms that link cancer remain incompletely understood. Psychological stressors initiate multiple physiological result activation hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system, subsequent changes immune function. disrupts homeostatic communication between neuroendocrine systems, shifting signaling toward proinflammatory state. Stress-induced low-grade inflammation decline surveillance both implicated progression. Conversely, tumor-induced inflammatory cytokines, apart from driving tumor-supportive microenvironment, also exert their biological actions distantly via circulation therefore adversely affect response. In this minireview, we summarize current findings on relationship focusing role stress-induced neuroendocrine-immune crosstalk. We discuss underlying potential treatment prevention.

Language: Английский

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α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 27, 2023

Abstract Depression is a common mental illness, which related to monoamine neurotransmitters and the dysfunction of cholinergic, immune, glutamatergic, neuroendocrine systems. The hypothesis one commonly recognized pathogenic mechanisms depression; however, drugs designed based on this have not achieved good clinical results. A recent study demonstrated that depression inflammation were strongly correlated, activation alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in system exhibited therapeutic effects against depression. Therefore, anti-inflammation might be potential direction for treatment Moreover, it also necessary further reveal key role α7 nAChR pathogenesis This review focused correlations between as well-discussed crucial CAP.

Language: Английский

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Inflammation as common link to progressive neurological diseases

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 98(1), P. 95 - 119

Published: Nov. 15, 2023

Abstract Life expectancy has increased immensely over the past decades, bringing new challenges to health systems as advanced age increases predisposition for many diseases. One of those is burden neurologic disorders. While hypotheses have been placed explain aging mechanisms, it widely accepted that increasing pro-inflammatory status with or “inflammaging” a main determinant biological aging. Furthermore, inflammaging at cornerstone age-related diseases and its involvement in disorders an exciting hypothesis. Indeed, development elderly seem share some basic pathways fundamentally converge on inflammation. Peripheral inflammation significantly influences brain function contributes neurological disorders, including Alzheimer’s disease, Parkinson’s multiple sclerosis. Understanding role pathogenesis progressive crucial importance developing effective treatments interventions can slow down prevent disease progression, therefore, decreasing social economic burden.

Language: Английский

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Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders

Neuronal Signaling, Journal Year: 2023, Volume and Issue: 7(4)

Published: Oct. 27, 2023

Abstract Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well when and how these experienced or expressed. It is focal overarching symptom in many severe prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit/hyperactivity disorder (ADHD), borderline personality (BPD). In all disorders, ED can manifest through symptoms depression, anxiety, affective lability. Considering symptomatic similarities between BD, ADHD, BPD, transdiagnostic approach promising lens investigation. Mounting evidence supports role peripheral inflammatory markers stress multifactorial aetiology physiopathology BPD. Of note, neural circuits that regulate appear particularly vulnerable to insults inflammation, impact neuroimmune milieu central nervous system. Thus far, few studies have examined link inflammation To our knowledge, no specific work has provided critical comparison results from disorders. fill this gap literature, we review known associations mechanisms linking general, clinically, BD. Our narrative begins an examination routes followed by discussion disorder-specific accounting for methodological limitations relevant confounding factors. Finally, critically discuss both correspondences discrepancies comment on potential vulnerability therapeutic interventions.

Language: Английский

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Structural and functional MRI correlates of inflammation in bipolar disorder: A systematic review

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 325, P. 83 - 92

Published: Jan. 5, 2023

Bipolar disorder (BD) is a common affective characterized by recurrent oscillations between mood states and associated with inflammatory diseases chronic inflammation. However, data on MRI abnormalities in BD their relationship inflammation are heterogeneous no review has recapitulated them. In this pre-registered (PROSPERO: CRD42022308461) systematic we searched Web of Science Core Collection PubMed for articles correlating functional or structural measures immune-related markers BD. We included 23 studies (6 functional, 16 findings, 1 both, including 1'233 patients). Overall, the quality was fair, low risk bias. Heterogeneity methods results small sample sizes limit generalizability conclusions. A qualitative synthesis suggests that links immune traits alterations point toward brain areas involved somatomotor processing, trend negative correlation peripheral regions volume. discuss how disentangling complex system may unveil mechanisms underlying symptoms pathophysiology, potentially quickly translatable diagnostic, prognostic, therapeutic implications.

Language: Английский

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