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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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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From Serendipity to Precision: Integrating AI, Multi-Omics, and Human-Specific Models for Personalized Neuropsychiatric Care

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 167 - 167

Published: Jan. 12, 2025

Background/Objectives: The dual forces of structured inquiry and serendipitous discovery have long shaped neuropsychiatric research, with groundbreaking treatments such as lithium ketamine resulting from unexpected discoveries. However, relying on chance is becoming increasingly insufficient to address the rising prevalence mental health disorders like depression schizophrenia, which necessitate precise, innovative approaches. Emerging technologies artificial intelligence, induced pluripotent stem cells, multi-omics potential transform this field by allowing for predictive, patient-specific interventions. Despite these advancements, traditional methodologies animal models single-variable analyses continue be used, frequently failing capture complexities human conditions. Summary: This review critically evaluates transition serendipity precision-based in research. It focuses key innovations dynamic systems modeling network-based approaches that use genetic, molecular, environmental data identify new therapeutic targets. Furthermore, it emphasizes importance interdisciplinary collaboration human-specific overcoming limitations Conclusions: We highlight precision psychiatry’s transformative revolutionizing care. paradigm shift, combines cutting-edge systematic frameworks, promises increased diagnostic accuracy, reproducibility, efficiency, paving way tailored better patient outcomes

Language: Английский

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Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 2096 - 2096

Published: Sept. 13, 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 the mass reduction seen in sarcopenia neuronal function characteristic neurodegeneration. Our limited understanding intricate relationships within this hinders accurate diagnosis effective treatment strategies. This review analyzes interrelated mechanisms contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, impaired nutrient delivery. aim is understand common pathways involved suggest comprehensive therapeutic approaches. dysfunctions hinder circulation transportation nutrients, resulting characterized by atrophy weakness. dysfunction have negative physical quality life. Neurodegenerative diseases exhibit comparable pathophysiological affect motor functions. Preventive approaches encompass lifestyle adjustments, addressing integrated therapies improving muscular well-being. Better links can refine strategies yield better patient outcomes. study emphasizes complex interplay between dysfunction, degeneration, decline, highlighting necessity for multidisciplinary Advances domain promise improved diagnostic accuracy, more options, enhanced preventive measures, all contributing higher life elderly population.

Language: Английский

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Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12767 - 12767

Published: Nov. 27, 2024

The tryptophan-kynurenine (KYN) pathway has long been recognized for its essential role in generating metabolites that influence various physiological processes. Traditionally, these have categorized into distinct, often opposing groups, such as pro-oxidant versus antioxidant, excitotoxic/neurotoxic neuroprotective. This dichotomous framework shaped much of the research on conditions like neurodegenerative and neuropsychiatric disorders, well cancer, where metabolic imbalances are a key feature. effects significantly influenced by factors, including concentration particular cellular milieu which they generated. A molecule acts neuroprotective at low concentrations may exhibit neurotoxic elevated levels. oxidative equilibrium surrounding environment can alter function KYN from an antioxidant to pro-oxidant. narrative review offers comprehensive examination analysis contemporary understanding metabolites, emphasizing their multifaceted biological functions relevance numerous pathological underscores pressing necessity paradigm shift comprehension metabolism. Understanding context-dependent roles is vital novel therapies Alzheimer's disease, multiple sclerosis, cancer. Comprehensive modulation, balancing inflammatory signals enzyme regulation, promising avenues targeted, effective treatments.

Language: Английский

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Sensory–movement underpinnings of lifelong neurodivergence: getting a grip on autism

Frontiers in Integrative Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 14, 2025

While the autism diagnosis emphasizes “deficits” in social communication, article advances that sensory–movement differences underpin through a review of following sources evidence. This account critically challenges “autistic regression”, with evidence features appear by birth as earliest signs and underlie behavioral used for diagnosis, which may reflect adaptations to inherent misunderstandings from others. Sensory motor are salient autistic people, but they often go underrecognized They cause cascading effects infancy on behavior communication sensorimotor learning, automatic imitation, eye contact, sensory perception, interests. The then explains how processing influence reduced perceptual narrowing, involves bottom-up information style grounded surrounding environment. Furthermore, this grow integration feedback loops potentially involving cerebellum brain. moves into implications widespread consequences these quality life. closes construct (including underestimated empathy pain), testing theory, providing sensory-sensitive support acceptance applications diverse people. theory apply particularly well women girls, people speech divergence, ADHD, co-occurring motor-related neurodivergences. Throughout article, also provides clinical, neurological, experiential lifelong, challenging notion “losing” (an) (diagnosis) instead reflecting (risky not necessarily “successful”) camouflaging.

Language: Английский

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Navigating Neurodegeneration: Integrating Biomarkers, Neuroinflammation, and Imaging in Parkinson’s, Alzheimer’s, and Motor Neuron Disorders

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1045 - 1045

Published: April 25, 2025

Neurodegenerative diseases represent a daunting global challenge, affecting millions worldwide and imposing significant clinical socioeconomic burdens [...]

Language: Английский

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Autism Spectrum Disorder Diagnosis Based on Attentional Feature Fusion Using NasNetMobile and DeiT Networks

Electronics, Journal Year: 2025, Volume and Issue: 14(9), P. 1822 - 1822

Published: April 29, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects social interactions, communication, and behavior. Prompt precise diagnosis essential for prompt support intervention. In this study, deep learning-based framework diagnosing ASD using facial images has been proposed. The methodology begins with logarithmic transformation image pre-processing, enhancing contrast making subtle features more distinguishable. Next, feature extraction performed NasNetMobile DeiT networks, where captures high-level abstract patterns, the network focuses on fine-grained characteristics relevant to identification. extracted are then fused attentional fusion, which adaptively assigns importance most discriminative features, ensuring an optimal representation. Finally, classification conducted bagging vector machine (SVM) classifier employing polynomial kernel, generalization robustness. Experimental results validate effectiveness of proposed approach, achieving 95.77% recall, 95.67% precision, 95.66% F1-score, accuracy, demonstrating its strong potential assisting in through analysis.

Language: Английский

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