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

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 26, 2024

Background: Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via Trp-kynurenine (KYN) metabolic pathway, producing a variety bioactive molecules. The aadat (kat2) gene encodes mitochondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little known about its role in behavior. Methods: CRISPR/Cas9-induced knockout (kat2^−/−) mice, we examined effects on emotion, memory, motor function, Trp metabolite levels, enzyme 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 levels generally consistent with those urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, indole-3-acetic lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase higher; oxidative excitotoxicity indices higher. Conclusion: show depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift toward KYN-3-HK partial gut microbial Trp-indole pathway metabolite. This first evidence that deleting causes unique despair experience, appears be excitatory neurotoxic stresses. may lead development double-hit preclinical model experience-based depression, better understanding these complex conditions, effective therapeutic strategies by elucidating relationship between PTSD pathogenesis.

Language: Английский

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Preservation of Vocal Function in Amyotrophic Lateral Sclerosis (ALS) Patients Following Percutaneous Dilatational Tracheostomy (PDT) and Adjuvant Therapies

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1734 - 1734

Published: Aug. 2, 2024

The study aimed to evaluate the efficacy of percutaneous dilatational tracheostomy (PDT) combined with adjuvant therapies in preserving vocal function amyotrophic lateral sclerosis (ALS) patients.

Language: Английский

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Dysregulated zinc homeostasis and microadenomas in the anterior pituitary: pathological insights into suicide risk

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

Published: Aug. 13, 2024

Background Suicide is a significant public health problem influenced by various risk factors, including dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Zinc (Zn), essential for pituitary function in hormone synthesis and release, has been linked to suicide, with studies noting reduced serum levels altered brain transport mechanisms. Despite Zn’s crucial role its involvement suicidal behavior, information on Zn suicide scarce. Tumor cells modify dynamics tissues, previous report suggests microadenomas anterior as factor suicide. Methods Histopathological analysis hematoxylin-eosin stain histochemical techniques assess homeostasis were carried out postmortem samples from 14 completers 9 non-suicidal cases. Results Pituitary identified 35% cases none Furthermore, compartmentalized (detected via dithizone reactivity), but not free zinquin was lower compared group. Conclusion This first potential association between disrupted feature provides critical insights future neuroendocrine Zn-related research.

Language: Английский

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In Vivo Prevalence of Beta-Amyloid Pathology and Alzheimer’s Disease Co-Pathology in Idiopathic Normal-Pressure Hydrocephalus—Association with Neuropsychological Features

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1898 - 1898

Published: Aug. 20, 2024

Idiopathic normal-pressure hydrocephalus (iNPH) is a clinic-radiological neurological syndrome presenting with cognitive deficits, gait disturbances and urinary incontinence. It often coexists Alzheimer's disease (AD). Due to the reversible nature of iNPH when promptly treated, lot studies have focused on possible biomarkers, among which are cerebrospinal fluid (CSF) biomarkers. The aim present study was determine rate beta-amyloid pathology AD co-pathology by measuring CSF namely, amyloid beta 42 40 amino acids (Aβ42), Aβ42/Aβ40 ratio, total Tau protein (t-Tau) phosphorylated at threonine 181 (p-Tau), in cohort patients, as well investigate associations biomarkers neuropsychological profiles. Fifty-three patients were included study. Aβ42, Aβ40, t-Tau p-Tau measured duplicate double-sandwich ELISA assays. evaluation consisted Mini-Mental State Examination, Frontal Assessment Battery, Five-Word Test CLOX drawing tests 1 2. After statistical analysis, we found that rather common higher values levels, existence profile, associated more severe memory impairment patients. In conclusion, our has confirmed AD-co-pathology markers worse decline these

Language: Английский

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Professor Klaus Fassbender: The Father of Mobile Stroke Units

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

Published: Sept. 10, 2024

Professor Klaus Fassbender is a distinguished neurologist from Germany, widely recognized for his groundbreaking contributions to the fields of neurology and neurodegenerative disease. His work has been pivotal in advancing our understanding pathophysiological mechanisms underlying disorders, including Alzheimer's Parkinson's disease, as well refining therapeutic strategies their treatment. studies cerebrovascular disease have elucidated complex molecular cellular processes involved ischemic hemorrhagic stroke, leading development novel interventions, often bridging gap between laboratory discoveries application clinical settings. "the father" mobile stroke unit (MSU). With "time brain" concept mind, he proposed developed MSU first time, allowing prehospital imaging, diagnosis, treatment directly at site emergency. This reduced times symptoms onset treatment, resulting an increased proportion patients receiving within golden hour" improvement functional outcomes 90 days. Fassbender's instrumental shaping contemporary approaches diagnosing managing making him figure modern neurology.

Language: Английский

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Biosafety Evaluation of a Chimeric Adenoviral Vector in Mini-Pigs: Insights into Immune Tolerance and Gene Therapy Potential

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2568 - 2568

Published: Nov. 9, 2024

The biosafety of gene therapy products remains a major challenge to their introduction into the clinic. In particular, problem immunogenicity viral vectors is focus attention. Large animals such as pigs, whose anatomical and physiological characteristics are similar those humans, have an advantage in testing vector systems.

Language: Английский

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Compound 21 Attenuates Isoflurane-Induced Injury in Neonatal Rat Hippocampal Neurons and Primary Rat Neuronal Cells by Upregulating METTL3

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 10079 - 10091

Published: Nov. 1, 2024

Isoflurane, as an anesthetic drug, has a neurotoxic effect on the developing brain tissue. Compound 21 (C21) been reported to be neuroprotective and ameliorate stroke effects. However, mechanism by which C21 protects against nerve damage remains unclear. Animal cellular models of injury were constructed using isoflurane (ISO) in neonatal SD rats primary rat neuronal cells (PRNCs). After treatment with C21, ultrastructure morphology hippocampus model assessed transmission electron microscope H&E staining. Methylation or apoptosis-related genes proteins examined immunohistochemistry, RT-qPCR, Western blot. The levels inflammatory factors monitored ELISA kits. m6A modification was analyzed Dot blot MeRIP-qPCR. Cell proliferation apoptosis also tested Edu TUNEL suppresses inflammation improves hippocampal ISO-induced rats. Mechanistically, upregulates modification, PPAR-a, BCL-2, METTL3 ISO-treated PRNCs. promotes cell proliferation, enhances BCL-2 reduces upregulating These findings suggest that survival up-regulates methylation Bc1-2 levels, potentially offering therapeutic strategy for neuroprotection clinical settings, particularly cases exposure. may related upregulation METTL3.

Language: Английский

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Enhancing Heart Rate-Based Estimation of Energy Expenditure and Exercise Intensity in Patients Post Stroke

Bioengineering, Journal Year: 2024, Volume and Issue: 11(12), P. 1250 - 1250

Published: Dec. 10, 2024

Indirect calorimetry is the gold standard field-testing technique for measuring energy expenditure and exercise intensity based on volume of oxygen consumed (VO Sixteen individuals post stroke completed treadmill walking exercises with concurrent indirect heart rate monitoring. Using 70% data, forward selection regression repeated k-fold cross-validation was used to build wVO Heart rate-based In people stroke,

Language: Английский

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Modern Psychiatry: from Theory to Practice

Personalized Psychiatry and Neurology, Journal Year: 2024, Volume and Issue: 4(4), P. 11 - 25

Published: Dec. 18, 2024

In this review scientific papers published on eLibrary, PubMed, Google Scholar were searched and analyzed for all time till 2024 year the problem of neuropsychiatry, translational neuro-science, biomarkers. The issues precision psychiatry targeted therapy mental disorders are considered. ways bridging gap between theoretical practical (clinical) discussed.

Language: Английский

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