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 DOI Creative Commons
Ágnes Szabó, Zsolt Galla, Eleonóra Spekker

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 26, 2024

Abstract 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.

Язык: Английский

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 DOI Creative Commons
Ágnes Szabó, Zsolt Galla, Eleonóra Spekker

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 26, 2024

Abstract 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.

Язык: Английский

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