Trends in research on novel antidepressant treatments

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 27, 2025

Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses a leading cause of disability worldwide. Key symptoms these conditions include depressed mood or anhedonia, sleep psychomotor disturbances, changes in appetite weight, fatigue loss energy. Prolonged cognitive disturbances further impair ability to think concentrate often accompanied by persistent feelings worthlessness excessive guilt. Collectively, underscore depression serious, long-term global health issue. In addition, clinical studies indicate growing number patients experiencing difficulties responding treatment, even long term. This phenomenon poses significant challenges for healthcare professionals, families, alike. As result, there is an urgent need therapies that both rapid-acting safe. review aims summarize prevailing trends research on novel antidepressants, emphasizing their diversity multi-directional mechanisms action. The development drugs increasingly focused achieving high efficacy, particularly treatment-resistant depression. Such advances offer potential rapid therapeutic effects without prolonged tedious administration older generation antidepressants. Findings from using animal models continue play crucial role predicting designing new strategies. These remain indispensable understanding physiological newly developed compounds, thereby guiding creation innovative treatments.

Language: Английский

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MCC950 Reduces the Anxiodepressive-like Behaviors and Memory Deficits Related to Paclitaxel-Induced Peripheral Neuropathy in Mice

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 143 - 143

Published: Jan. 25, 2025

Chemotherapy-induced peripheral neuropathy and the accompanying affective disorders are serious side effects, their resolution is not guaranteed. Oxidative stress elevated levels of Nod-like receptor protein 3 (NLRP3) have been detected in central nervous systems animals with neuropathic pain provoked by several antineoplastic drugs, such as paclitaxel (PTX). Several studies further indicated that NLRP3 inflammasome inhibition could be an approach for treating chronic pain, but its impact on anxiodepressive-like behaviors memory deficits related to PTX-provoked has yet investigated. MCC950 a potent specific inhibitor pathway acts through inhibiting activation formation. We hypothesized administration alleviate cognitive neuropathy. Using male C57BL/6 mice, we assessed effects mechanical thermal allodynia, behavior, incited this taxane. The results intraperitoneal 10 mg/kg twice daily three consecutive days fully reversed PTX-induced allodynia. This treatment also completely attenuated anxiolytic (p < 0.004) depressive-like 0.022) (novel object recognition test; p 0.0018) PTX. These actions were mainly achieved blocking sciatic nerve, amygdala, hippocampus, oxidative amygdala hippocampus. normalized p-ERK 1/2 overexpression nerve apoptotic responses amygdala. study suggests might promising mental illnesses

Language: Английский

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Understanding Role of Maternal Separation in Depression, Anxiety,and Pain Behaviour: A Mini Review of Preclinical Research With Focus on Neuroinflammatory Pathways

International Journal of Developmental Neuroscience, Journal Year: 2025, Volume and Issue: 85(1)

Published: Feb. 1, 2025

Contact between mother and child is essential for the proper development of an infant's physiological systems, brain maturation behavioural outcomes. Early life stress (ELS), which includes factors such as inadequate parental care childhood abuse, significantly increases risk developing neuropsychiatric disorders, including anxiety depression. This review examines impact maternal separation (MS) on depression, pain behaviour, with a particular emphasis neuroinflammatory pathways. Experiences ELS can adversely affect neurotransmitter systems associated neural circuits that are crucial processing painful stimuli regulating Stressful experiences trigger inflammatory processes in brain, initiating immune responses cells stimulating production pro-inflammatory cytokines. In mammals, MS serves significant stressor activates hypothalamic-pituitary-adrenal (HPA) axis other stress-related leading to increased challenges heightened sensitivity adulthood due systemic inflammation. Key mediators, IL-1β, IL-6 TNF-α, play critical roles pathological pain, while activation microglia releases mediators contribute neurological dysfunction pathophysiology stress, depression anxiety. Moreover, therapeutics targeting oxidative inflammation have shown promise alleviating affective disorders following MS. discusses potential pathways, primary focus mechanisms therapeutic strategies may mitigate adverse effects There pressing need further research elucidate underlying pathways identify effective interventions improve mental health outcomes individuals affected by

Language: Английский

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Role of microbiota in pain: From bench to bedside

iMetaOmics., Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract Interactions between the microbiota and host have been proven to be critical regulators of homeostasis, pain perception is no exception. Emerging evidence has identified mechanisms by which dysbiosis contributes hyperalgesia revealed potential value microbiota‐associated therapies in management. Herein, authors introduce basic knowledge for readers who are not simultaneously majoring these two fields. The clarified underlying regulation outlined terms three ways. This review summarizes current advancements management microbiology research clinicians wish focus on this area. Probiotics, fecal transplantation, other methods modulation entered clinical translation. further propose present limitations prospects high‐quality development preclinical investigations. Importantly, despite large amount attention given gut bacteria, also puts forward great expectations role nongut nonbacterial sensation. Efforts decipher functions will help promote achievements from bench bedside.

Language: Английский

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Mental Health Disorders Due to Gut Microbiome Alteration and NLRP3 Inflammasome Activation After Spinal Cord Injury: Molecular Mechanisms, Promising Treatments, and Aids from Artificial Intelligence

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 197 - 197

Published: Feb. 14, 2025

Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these gut dysbiosis (GD) and the activation of NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are special interest for their roles in impacting mental health. Studies found state microbiome is thrown into disarray after SCI, providing a chance GD occur. Metabolites such as short-chain fatty acids (SCFAs) variety neurotransmitters produced hampered GD. This disrupts healthy cognitive processes opens door SCI patients impacted health disorders. Additionally, some studies an increased presence NLRP3 respective parts patients. Preclinical clinical shown plays key role maturation pro-inflammatory cytokines initiate eventually aggravate disorders In addition mechanisms intensifying this review article further focuses on promising treatments: fecal transplants, phytochemicals, melatonin. treatments effective combating pathogenic inflammasome, well alleviating symptoms may Another area focus exploring how artificial intelligence (AI) used support treatments. AI models already developed track changes microbiome, simulate drug-gut interactions, design novel anti-NLRP3 peptides. While promising, research applications treatment needed.

Language: Английский

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FOXO3-induced microRNA-128-3p promotes the progression of spinal cord injury in mice via regulating NLRP3 inflammasome-mediated pyroptosis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 21, 2025

Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate and complex pathophysiologic mechanisms. Pyroptosis, inflammatory form of cell death triggered by certain inflammasomes, has key role in variety diseases, including SCI. However, it is unclear whether microRNAs (miRNAs), novel regulators the SCI, are involved SCI-induced pyroptosis. Two GEO miRNA expression profiles (GSE158195 GSE90452) were downloaded, differentially expressed miRNAs analyzed bioinformatics methods. An vivo animal model vitro cellular SCI constructed female C57BL/6 mice BV-2 cells for studying possible roles FOXO3, miR-128-3p NLRP3-mediated pyroptosis Markers ROS, inflammation measured RT-qPCR, Western blotting, immunofluorescence, flow cytometry, enzyme-linked immunosorbent assays. Histopathological changes spinal tissue detected using hematoxylin eosin immunohistochemical. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate motor function each group. Bioinformatics analysis GSE158195 GSE90452 datasets revealed significant downregulation miR-128-3p, phenomenon that consistently observed model. Functionally, upregulation improved functional behavioral recovery, relieved pathological injury, repressed oxidative stress, alleviated mouse models. We also confirmed Thioredoxin-interacting protein (TXNIP) target gene overexpression TXNIP can effectively reverse improvement Moreover, we found transcription factor FOXO3 facilitated expression, its resulted similar effects To best our knowledge, this first report demonstrating secondary through modulation pathway. Our results suggest FOXO3/miR-128-3p/TXNIP/NLRP3-mediated axis may be potential therapeutic

Language: Английский

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Self‐Enhancing Drug Pair‐Driven Selenium Nanotherapeutics Reverses Microglial Pyroptosis Through NLRP3/Caspase‐1 Pathway and Neuronal Apoptosis for Treatment of Spinal Cord Injury

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

Abstract Spinal cord injury (SCI) constitutes a critical occurrence that results in the disruption of both motor and sensory functions. Oxidative stress‐induced apoptosis pyroptosis have been identified as contributors to neuronal damage during secondary phase following SCI. Therefore, this study focuses on development self‐enhancing drug pair‐driven selenium (Se) nanotherapeutics, loading with 2,3,5,6‐tetramethylpyrazine (TMP) Ginsenoside Rg1 (Rg1), enhance treatment The engineered LET/TMP/Rg1@Se NPs exhibits remarkable antioxidant properties, effectively reducing oxidative by minimizing reactive oxygen species (ROS) accumulation restoring mitochondrial function. In addition their effects, nanotherapeutics demonstrates significant anti‐pyroptotic effects BV2 microglial cells modulating NLRP3/caspase‐1 pathway, leading decreased release pro‐inflammatory cytokines IL‐1β IL‐18. Moreover, inhibition inflammatory cascade response diminishes neuroinflammation‐induced promotes axonal regeneration neurons vitro. mouse model SCI, improved function regeneration, attributed pyroptosis, highlighting scientific basis for synergistic effect Se an innovative strategy effective SCI therapy.

Language: Английский

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Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 25, 2025

Neuropathic pain (NP) is a common symptom of many diseases and caused by direct or indirect damage to the nervous system. Tricyclic antidepressants serotonin-norepinephrine reuptake inhibitors are typical drugs used in clinical practice suppress pain. However, these have drawbacks, including short duration action, limited analgesic effect, possible dependence side effects. Therefore, developing more effective NP treatment strategies has become priority medical research attracted much attention. P2X7 receptor (P2X7R) non-selective cation channel activated adenosine triphosphate mainly expressed microglia central Microglial P2X7R plays an important role regulation, suggesting that it could be potential target for drug development. This review comprehensively objectively discussed latest progress P2X7R, its structural characteristics, functional properties, relationship with microglial activation polarization, mechanism therapeutic multiple models. study aimed provide in-depth insights into association between explore action pathological process translational application prospects antagonists treatment, providing scientific basis precise NP.

Language: Английский

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Acellular spinal cord scaffold containing quercetin-encapsulated nanoparticles plays an anti-inflammatory role in functional recovery from spinal cord injury in rats

Inflammopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: May 3, 2024

Language: Английский

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A novel anti-inflammatory strategy for myocardial ischemia–reperfusion in rats with cinnamamide derivative compound 7

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 136, P. 112370 - 112370

Published: May 31, 2024

Language: Английский

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