Molecular pathways of major depressive disorder converge on the synapse

Molecular Psychiatry, Год журнала: 2022, Номер 28(1), С. 284 - 297

Опубликована: Окт. 6, 2022

Abstract Major depressive disorder (MDD) is a psychiatric disease of still poorly understood molecular etiology. Extensive studies at different levels point to high complexity numerous interrelated pathways as the underpinnings depression. systems under consideration include monoamines, stress, neurotrophins and neurogenesis, excitatory inhibitory neurotransmission, mitochondrial dysfunction, (epi)genetics, inflammation, opioid system, myelination, gut-brain axis, among others. This review aims illustrating how these multiple signaling may interact provide more comprehensive view MDD’s neurobiology. In particular, considering pattern synaptic activity closest physical representation mood, emotion, conscience we can conceptualize, each pathway or system will be scrutinized for links neurotransmission. Models neurobiology MDD discussed well future actions improve understanding treatment options.

Язык: Английский

---

The Role of Microglia in Brain Metastases: Mechanisms and Strategies

Aging and Disease, Год журнала: 2024, Номер 15(1), С. 169 - 169

Опубликована: Янв. 1, 2024

Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung melanoma at a high risk developing brain metastases. However, mechanisms underlying metastatic cascade remain poorly understood. Microglia, resident macrophages parenchyma, involved multiple processes associated metastasis, including inflammation, angiogenesis, immune modulation. They also closely interact cancer cells, astrocytes, other cells. Current therapeutic approaches against cancers, small-molecule drugs, antibody-coupled drugs (ADCs), immune-checkpoint inhibitors (ICIs), have compromised efficacy owing to impermeability blood-brain barrier (BBB) complex microenvironment. Targeting microglia is strategies for treating In this review, we summarize multifaceted roles highlight them as potential targets future interventions.

Язык: Английский

---

The molecular pathophysiology of depression and the new therapeutics

MedComm, Год журнала: 2022, Номер 3(3)

Опубликована: Июль 21, 2022

Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand molecular pathophysiology of depression, it still unclear. Current treatments for depression are inadequate individuals, because limited effectiveness, delayed efficacy (usually two weeks), side effects. Consequently, novel drugs with increased speed action effectiveness required. Ketamine has shown have rapid, reliable, long-lasting antidepressant effects in treatment-resistant MDD patients represent breakthrough therapy MDD; however, concerns regarding its efficacy, potential misuse, remain. In this review, we aimed summarize mechanisms pharmacological depression. We focused on fast treatment clarified safety, tolerability, ketamine metabolites treatment, along review mechanisms, research challenges, future clinical prospects.

Язык: Английский

---

Astrocytes and major depression: The purinergic avenue

Neuropharmacology, Год журнала: 2022, Номер 220, С. 109252 - 109252

Опубликована: Сен. 16, 2022

Язык: Английский

---

The brain-gut-microbiota interplay in depression: A key to design innovative therapeutic approaches

Pharmacological Research, Год журнала: 2023, Номер 192, С. 106799 - 106799

Опубликована: Май 19, 2023

Depression is the most prevalent mental disorder in world associated with huge socio-economic consequences. While depressive-related symptoms are well known, molecular mechanisms underlying disease pathophysiology and progression remain largely unknown. The gut microbiota (GM) emerging as a key regulator of central nervous system homeostasis by exerting fundamental immune metabolic functions. In turn, brain influences intestinal microbial composition through neuroendocrine signals, within so-called microbiota-brain axis. balance this bidirectional crosstalk important to ensure neurogenesis, preserve integrity blood-brain barrier avoid neuroinflammation. Conversely, dysbiosis permeability negatively affect development, behavior, cognition. Furthermore, although not fully defined yet, changes GM depressed patients reported influence pharmacokinetics common antidepressants affecting their absorption, metabolism, activity. Similarly, neuropsychiatric drugs may shape turn an impact on efficacy toxicity pharmacological intervention itself. Consequently, strategies aimed at re-establishing correct homeostatic (i.e., prebiotics, probiotics, fecal transplantation, dietary interventions) represent innovative approach improve pharmacotherapy depression. Among these, probiotics Mediterranean diet, alone or combination standard care, hold promise for clinical application. Therefore, disclosure intricate network between depression will give precious insights diagnostic therapeutic approaches towards depression, profound implications drug development practice.

Язык: Английский

---

Folate and Its Significance in Depressive Disorders and Suicidality: A Comprehensive Narrative Review

Nutrients, Год журнала: 2023, Номер 15(17), С. 3859 - 3859

Опубликована: Сен. 4, 2023

Depressive disorders pose significant challenges to global public health, necessitating effective prevention and management strategies. Notably, the occurrence of suicide frequently coincides with depressive episodes. Suicide is as a paramount health concern that demands efficacious preventive Current psychiatric approaches heavily rely on pharmacological interventions but have had limited success in addressing burden mental issues. Suboptimal nutrition, its impact neuroendocrine system, has been implicated underlying pathology disorders. Folate, group water-soluble compounds, plays crucial role various central nervous system functions. Depressed individuals often exhibit low levels serum red blood cell folate. Multiple studies systematic reviews investigated efficacy folic acid derivative, L-methylfolate, which can cross blood–brain barrier, stand-alone or adjunct therapies for depression. Although findings mixed, available evidence generally supports use these compounds depressed individuals. Recent established links between one-carbon cycle, folate–homocysteine balance, immune function, glutamate excitation via NMDA (N-methyl-D-aspartate) receptors, gut microbiome eubiosis mood regulation. These provide insights into complex neurobiological mechanisms effects folate related Through comprehensive review existing literature, this study aims advance our understanding therapeutic potential depression treatment. It also seeks explore their suicidal tendencies shed light involved, leveraging latest discoveries research.

Язык: Английский

---

Verbascoside: A neuroprotective phenylethanoid glycosides with anti-depressive properties

Phytomedicine, Год журнала: 2023, Номер 120, С. 155027 - 155027

Опубликована: Авг. 18, 2023

Язык: Английский

---

“Inflamed” depression: A review of the interactions between depression and inflammation and current anti-inflammatory strategies for depression

Pharmacological Research, Год журнала: 2024, Номер 207, С. 107322 - 107322

Опубликована: Июль 20, 2024

Depression is a common mental disorder, the effective treatment of which remains challenging issue worldwide. The clinical pathogenesis depression has been deeply explored, leading to formulation various pathogenic hypotheses. Among these, monoamine neurotransmitter hypothesis holds prominent position, yet it significant limitations as more than one-third patients do not respond conventional treatments targeting transmission disturbances. Over past few decades, growing body research highlighted link between inflammation and potential key factor in pathophysiology depression. In this review, we first summarize relationship depression, with focus on pathophysiological changes mediated by mechanisms linking well multiple anti-inflammatory strategies are also discussed, their efficacy safety assessed. This review broadens perspective specific aspects using for treating laying groundwork advancing precision medicine individuals suffering from "inflamed"

Язык: Английский

---

Age-related impact of social isolation in mice: Young vs middle-aged

Neurochemistry International, Год журнала: 2024, Номер 174, С. 105678 - 105678

Опубликована: Янв. 23, 2024

Social isolation is a chronic mild stressor and significant risk factor for mental health disorders. Herein we explored the impact of social on depression- anxiety-like behaviours, as well spatial memory impairments, in middle-aged male mice compared to post-weaning mice. We aimed quantify correlate isolation-induced behaviour discrepancies with changes hippocampal glial cell reactivity pro-inflammatory cytokine levels. Post-weaning C57BL7/J6 were socially isolated 3-week period behavioural tests performed last five days isolation. found that 3 weeks led depressive-like forced swim test, open field impairment Morris water maze paradigm These alterations not observed after isolation, indicating resilience isolation-mediated stress. Increased Iba-1 expression NLRP3 priming both hippocampus mice, suggesting role microglia pathway detrimental effects cognition behaviour. Young also demonstrated elevated controls, but no differences levels Ageing-induced activation enhancement IL-1β, TNF-α IL-6 proinflammatory cytokines, known signs low-grade inflammatory state, detected. Altogether, data suggest addition inflammaging, contributes stress-related cognitive

Язык: Английский

---

Costunolide normalizes neuroinflammation and improves neurogenesis deficits in a mouse model of depression through inhibiting microglial Akt/mTOR/NF-κB pathway

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Abstract Neuroinflammation is crucial for the pathogenesis of major depression. Preclinical studies have shown potential anti-inflammatory agents, specifically costunolide (COS), correlate with antidepressant effects. In this study, we investigated molecular mechanisms underlying actions COS. Chronic restraint stress (CRS) was induced in male mice. The mice were treated either intra-DG injection COS (5 μM, 1 μL per side) or (20 mg/kg, i.p.) week. We showed that administration through both routes significantly ameliorated depressive-like behavior CRS-exposed Furthermore, improved chronic stress-induced adult hippocampal neurogenesis deficits attenuating microglia-derived neuroinflammation. demonstrated μM) exerted anti-neuroinflammatory effects LPS-treated BV2 cells via inhibiting microglial Akt/mTOR/NF-κB pathway; inactivation mTOR/NF-κB/IL-1β pathway required pro-neurogenic action Our results reveal mechanism normalizing neuroinflammation to improve deficits, supporting agents as a therapeutic strategy

Язык: Английский

---