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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The Indissociable Triad: Vascular Impairment, Muscle Atrophy, and Cognitive Decline

Published: Aug. 12, 2024

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating mass reduction seen in sarcopenia the neuronal functions characteristic neurodegeneration. Our limited understanding intricate relationships within this hinders accurate diagnosis effective treatment strategies. This review ana-lyzes interrelated mechanisms contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, impaired nutrient delivery. aim is understand common pathways involved suggest comprehensive therapeutic approaches. dysfunctions hinder circulation transportation nutrients, resulting sar-copenia characterized by atrophy weakness. dysfunction have negative physical function quality life. Neurodegenerative diseases exhibit comparable pathophysiological affect motor functions. Preventive approaches encompass lifestyle adjustments, addressing oxidative in-flammation, integrated therapies improving muscular well-being. Better links can refine strategies yield better patient out-comes. study emphasizes complex interplay between dysfunction, de-generation, decline, highlighting necessity for multidisciplinary ap-proaches. Advances domain promise improved diagnostic accuracy, more thera-peutic options, enhanced preventive measures, all contributing higher life elderly population.

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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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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Developments, Hardships, and Prospective Directions in the Field of Neuroscience and Neurological Machine Learning for Behavioral Evaluation

Advances in psychology, mental health, and behavioral studies (APMHBS) book series, Journal Year: 2025, Volume and Issue: unknown, P. 459 - 474

Published: Jan. 3, 2025

This study examines the current state of neuroscience, emphasizing use machine learning to improve behavioral assessment and its therapeutic applications. Progress in neuroscience has facilitated comprehension cognitive aging, neurological illnesses, essential function cognition detecting decline. The increasing potential likely overcomes aforementioned deficiencies—consistent monitoring early identification mental health—through automation. research will ultimately address AI-related concerns regarding longitudinal individuals with illnesses. Neurocognitive testing may leverage significantly advance evaluation management health, hence facilitating future enhance broaden capabilities neurolearning neuropsychology.

Language: Английский

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Bibliometric Analysis of Neuroinflammation and Postoperative Cognitive Dysfunction

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

ABSTRACT Background The occurrence and development of postoperative cognitive dysfunction (POCD) are closely linked to neuroinflammation. This bibliometric analysis aims provide novel insights into the research trajectory, key topics, potential future trends in field neuroinflammation‐induced POCD. Methods Web Science Core Collection (WoSCC) database was searched identify publications from 2012 2023 on Bibliometric analysis, involving both statistical visual analyses, conducted using CiteSpace, VOSviewer, R software. Results Research POCD has exhibited an increasing trend over past 12 years. China had highest number publications, Nanjing Medical University most collaboration with other institutions, Zhiyi Zuo published author, Journal Neuroinflammation served as primary publication frequent keyword Keyword clustering indicated that predominant cluster is dexmedetomidine. Burst detection revealed delirium (POD), perioperative neurocognitive disorders (PND), apoptosis, epigenetic modifications were trends. Conclusions Our identified following areas associated POCD: anesthesia, surgery, dexmedetomidine, NLRP3 inflammasome, mechanism topics comprise POD, PND, modifications.

Language: Английский

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Psychedelics in neuroinflammation: Mechanisms and therapeutic potential

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111278 - 111278

Published: Jan. 1, 2025

Language: Английский

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The Relationship Between Grip Strength and Cognitive Impairment: Evidence From NHANES 2011–2014

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

ABSTRACT Background Prior research has consistently shown an association between muscle strength and various metabolic diseases. However, the relationship cognitive impairment remains elusive. Methods Using data from 2011–2014 National Health Nutrition Examination Survey (NHANES), we investigated impairment. We used multivariate logistic regression, restricted cubic spline regression (RCS), threshold effects to investigate impact of on function. In addition, analyzed correlation in subgroups age, gender, race, education, smoking status, drinking hypertension, diabetes, heart disease. Results 2124 participants were ultimately included for further analysis. Multivariate trend testing, RCS analysis showed a non‐linear negative Threshold effect suggests that when reaches certain value, this undergoes significant changes. three function scoring tests, interaction was only observed racial subgroup. Conclusion This study function, which may have effect. Further longitudinal studies are needed elucidate its potential mechanisms.

Language: Английский

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Individual differences in intracortical inhibition predict action control when facing emotional stimuli

Frontiers in Psychology, Journal Year: 2024, Volume and Issue: 15

Published: June 12, 2024

Efficient inhibitory control in the context of prepotent actions is vital. However, such action inhibition may be profoundly influenced by affective states. Interestingly, research indicates that can either impaired or improved emotional stimuli. Thus, a great deal confusion surrounds our knowledge complex dynamics subtending emotions and control. Here, we aimed to investigate whether negative stimuli, even when non-consciously presented task-irrelevant, affect relative neutral Additionally, tested individual differences intracortical excitability predict capabilities. To address these issues, asked participants complete modified version Stop Signal Task (SST) which fearful stimuli were subliminally before go signals as primes. Moreover, assessed participants’ resting-state corticospinal excitability, short (SICI), facilitation (ICF). Results demonstrated better capabilities interindividual SICI predicted stronger Taken together, results shed new light on intricate between action, consciousness, motor control, suggesting measures used potential biomarkers reduced clinical settings.

Language: Английский

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Exploring Cognitive Impairments Associated with Primary Open-Angle Glaucoma and Exfoliation Glaucoma

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1706 - 1706

Published: Aug. 1, 2024

This study explored the link between different types of glaucoma and cognitive function in a cohort 620 Japanese patients. Participants were categorized into primary open-angle (PG), exfoliation (EG), non-glaucomatous control groups. The findings revealed significant decline as indicated by Mini-Cog test EG group (mean ± SD: 4.0 1, 95% CI: 3.9 to 4.2) compared PG (4.4 0.1, 4.3 4.5,

Language: Английский

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