Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Language: Английский

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Navigating the Neurobiology of Migraine: From Pathways to Potential Therapies

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1098 - 1098

Published: June 25, 2024

Migraine is a debilitating neurological disorder characterized by recurring episodes of throbbing headaches that are frequently accompanied sensory disturbances, nausea, and sensitivity to light sound [...]

Language: Английский

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Revolutionizing our understanding of Parkinson’s disease: Dr. Heinz Reichmann’s pioneering research and future research direction

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(12), P. 1367 - 1387

Published: Aug. 7, 2024

Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, distinguished professor neurologist, has made substantial advancements in domain PD research, encompassing both fundamental scientific investigations practical applications. His research illuminated etiology treatment PD, as well function energy metabolism premotor symptoms. As precursor to number neurotransmitters neuromodulators that implicated pathophysiology he also investigated application tryptophan (Trp) derivatives disease. principal findings insights summarized synthesized this narrative review article, which emphasizes challenges implications for future research. This aims identify analyze key contributions Reichmann field ultimate goal informing directions domain. By examining Reichmann's work, study seeks provide comprehensive understanding his major how they can be applied advance diagnosis PD. paper explores potential intersection emerging avenues, such investigation Trp its metabolites, particularly kynurenines, could lead new therapeutic strategies managing disorders like

Language: Английский

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Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence

Nutrients, Journal Year: 2024, Volume and Issue: 16(16), P. 2721 - 2721

Published: Aug. 15, 2024

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant anti-inflammatory properties, has emerged as promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms curcumin’s effects optimal dosages different conditions necessitate further investigation. This systematic review synthesizes current evidence on potential addressing disorders, emphasizing its impact cognitive function, neurodegeneration, muscle health older adults. By evaluating safety, efficacy, action curcumin supplementation, this aims provide insights into therapeutic promoting healthy aging. A search across three databases using specific keywords yielded 2256 documents, leading selection 15 clinical trials synthesis. Here, we highlight multifaceted agent combating disorders. The findings suggest that could offer effective approach enhancing quality life aging individuals. Further research well-designed are essential validate optimize use personalized medicine approaches conditions.

Language: Английский

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Efficacy of Ginkgo biloba as an adjunct to donepezil in amyloid PET-positive Alzheimer’s patients

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

Published: March 11, 2025

Background Ginkgo biloba is widely used in some regions as an adjunct therapy for Alzheimer’s disease (AD). Its potential mechanisms include antioxidative and anti-amyloid properties, yet clinical evidence remains mixed. Objective We investigated whether combining with donepezil confers additional benefits amyloid PET-positive AD patients. also explored changes the plasma biomarker MDS-Oaβ (Multimer Detection System–Oligomeric Aβ), which reflects propensity of Aβ monomers to form oligomers. Methods This retrospective study included newly diagnosed, drug-naïve patients who were had at least 12 months follow-up. Participants received either alone (Donepezil-only) or plus (Donepezil-Ginkgo). Clinical measures Korean version Mini-Mental State Examination (K-MMSE) Sum Boxes Dementia Rating (CDR-SB). Plasma was assessed baseline months. Results A total 101 analyzed (60 Donepezil-only, 41 Donepezil-Ginkgo). Baseline demographics characteristics similar. After months, Donepezil-only group showed minimal change K-MMSE a slight decrease MDS-Oaβ. The Donepezil-Ginkgo demonstrated significant improvement (+2.4) larger reduction (−0.15). No between-group difference observed CDR-SB. Adverse events mostly mild did not lead discontinuation. Conclusion addition may yield superior cognitive outcomes greater compared Further large-scale, prospective trials are warranted validate these findings elucidate Ginkgo’s mechanistic role AD.

Language: Английский

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Environmental Factors in the Etiology of Mental Disorders in the Czech Republic: Final Results

Neuropsychiatric Disease and Treatment, Journal Year: 2025, Volume and Issue: Volume 21, P. 541 - 545

Published: March 1, 2025

Language: Английский

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Saffron’s promise: a systematic review of its role in Alzheimer's treatment

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Journal Year: 2025, Volume and Issue: 61(1)

Published: March 24, 2025

Abstract Alzheimer’s disease (AD) is the most common form of dementia, which can be debilitating and affect patients’ quality life. Saffron ( Crocus Sativus L.) a plant growing in various countries with potential anti-inflammatory, antioxidant effects. This study aims to systematically review role saffron as therapeutic agent or supplementation patients AD. We searched PubMed, Scopus, Embase, Web Science databases on 5/1/2023. Clinical studies that reported effectiveness and/or safety AD are considered for inclusion. 565 were identified initial comprehensive search, finally, only 4 met eligibility criteria. All conducted Iran. Studies showed has comparable efficacy cognitive outcomes approved drugs AD, donepezil, memantine; however, does not add beneficial effects this regard. There no considerable issues. suggested herbal based limited available evidence. Limitations evidence such small sample sizes well skimp number included prudence clinical recommendations findings study; systematic shed light necessity conducting future trials topic.

Language: Английский

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Ginkgolide B Inhibits EMT and Promotes Pyroptosis in Gastric Cancer via AKT/mTOR Pathway

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 2491 - 2502

Published: April 1, 2025

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration novel therapeutic agents to improve patient outcomes. This study elucidates anti-cancer properties Ginkgolide B (GGB), diterpenoid lactone derived from Ginkgo biloba, in both vitro and vivo models GC. Using AGS HGC-27 cell lines, we assessed GGB's impact on cellular proliferation, colony formation, migration, invasion, apoptosis, pyroptosis. GGB exhibited significant dose- time-dependent inhibition proliferation with no cytotoxicity observed normal gastric epithelial cells. Furthermore, markedly suppressed migration induced apoptosis pyroptosis, as evidenced by increased Bax GSDMD expression decreased Bcl-2 levels. In vivo, treatment significantly reduced tumor growth nude mouse xenograft model modulated EMT markers, decreasing PCNA N-cadherin levels while increasing E-cadherin expression. Mechanistically, effects were mediated through deactivation PI3K/AKT/mTOR signaling pathway. These findings underscore potential promising agent for GC, warranting further clinical evaluation.

Language: Английский

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Targeting Platelet Activating Factor Signaling for Therapeutic Benefits in Neurodegenerative Disorders

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(4)

Published: April 23, 2025

Neurodegenerative disorders (NDs), including dementia, Alzheimer’s disease (AD), and Parkinson’s (PD), are age-related diseases closely associated with chronic inflammation, oxidative stress, gene mutations, autoimmune-derived other external risk factors. They characterized by progressive neuronal loss, cognitive decline, and/or motor dysfunction, inflammation being a key player in intensifying NDs’ occurrence. One of the most important molecular inflammatory mediators linking to NDs is platelet-activating factor (PAF) its pivotal signaling for regulating neuroinflammation, apoptosis, damage. Dysregulation PAF activity metabolism/levels, along overexpression receptor (PAF-R) have been exacerbated responses, further aggravating neurodegeneration. This article highlights role neurodegeneration, particular focus on novel insights into potential medicinal use inhibitors prevention treatment neurodegenerative diseases. We evaluate recently proposed concept targeting pathway through either natural synthetic or combination both. It explores these offer significant preventative therapeutic benefits against NDs, likely anti-inflammatory anti-aging effects slowing down progression preserving dysfunction. Current status future perspectives such approaches also discussed.

Language: Английский

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Anthocyanin supplementation in adults at risk for dementia: a randomized controlled trial on its cardiometabolic and anti-inflammatory biomarker effects

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Abstract Anthocyanins are dietary flavonoids shown to have a therapeutic capacity mitigate inflammation and oxidative stress. The present secondary analyses from the “Anthocyanins in People at Risk for Dementia Study” were aimed (I) determining intervention’s effect on blood-based markers of cardiovascular disease (II) evaluating whether baseline factors such as age, sex, inflammation, or cardiometabolic score may moderate inflammatory status. This study was an ancillary, 24-week randomized, double-blind, placebo-controlled Phase II trial. Sub-sample participants ( n = 99), aged 60–80 years with mild cognitive impairment disorders, randomized receive either 320 mg/day anthocyanins placebo. biomarkers analyzed included biomarker assessment (IL − 6, IL 8, 10, 1b, TNF α, IFN γ), C-reactive protein (CRP), well albumin, thrombocytes, cholesterol, LDL, HDL, triglycerides, which longitudinally compared between both groups. Baseline characteristics balanced ANCOVA reveal differences favoring anthocyanin treatment LDL cholesterol levels (ƞp 2 0.078; p 0.015), 0.073; 0.021), CRP 0.417; 0.0001), 6 (ƞp2 0.085; 1b 0.058; 0.037), Inflam z-score 5 0.059, 0.004). Moderation analysis demonstrated that significant predictor intervention levels. Anthocyanin supplementation reduces individuals risk dementia, especially when there is increased baseline. ClinicalTrials.gov identifier: NCT03419039.

Language: Английский

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