Kynurenine Aminotransferase II Knockout Mice Mimic Depression with Psychomotor Retardation

Ágnes Szabó; Eleonóra Spekker; József Toldi; Masaru Tanaka; Etsuro Ono; László Vécsei

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Kynurenine Aminotransferase II Knockout Mice Mimic Depression with Psychomotor Retardation

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¹ Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
² Doctoral School of Clinical Medicine, University of Szeged, Korányi fasor 6, H-6720 Szeged, Hungary
³ ELKH-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
⁴ Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary
⁵ Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
⁶ Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Academic Editor: Kenji Hashimoto

Published: 21 April 2023 by MDPI in The 2nd International Electronic Conference on Biomedicines session Molecular Mechanisms of Neurodegeneration

https://doi.org/10.3390/ECB2023-14364 (registering DOI)

Abstract:

Major depressive disorder (MDD) exhibits negative emotional symptoms with various degrees of psychomotor manifestation. The disturbance of the tryptophan-kynurenine (KYN) metabolic system has been implicated in MDD. Kynurenine/α-aminoadipate aminotransferase (KAT II) is a mitochondrial enzyme that catalyzes the reaction of KYN to kynurenic acid. Little is known about the impact of the gene aadat knockout (KAT II KO^-/-) on behaviors. We studied negative emotional and motor domains at 4 and 12 weeks of male KAT II KO^-/- mice and the wild-type counterpart C57BL/6N.

Depression-like, anxiety-like, and motor behaviors were assessed by modified forced swim test (FST), elevated plus-maze (EPM) test, light-dark box (LDB) test, and open field (OF) test.

FST showed significantly more depression-like behaviors at 4 and 12 weeks in KAT II KO^-/-mice than the wild-type and the older mice were more prominent in both strains. Both strains spent significantly more time in the light at week 12 than week 4 in LDB test. The OF test showed significantly shorter ambulation time at week 12 in KAT II KO^-/-mice than the wild-type and significantly longer time spent in the center zone at week 12 than week 4 in both strains.

We show here that KAT II KO^-/- mice exhibit more depression-like behaviors in an age-dependent manner, accompanied with decreasing anxiety and motor activity. Thus, the aadat gene knock-out influences behavioral domains in such a manner that the strain potentially serves as an animal model of a subtype, depression with psychomotor retardation.

Keywords: depression; anxiety, motor function; tryptophan; kynurenine; kynurenine aminotransferase; psychomotor; animal model; forced swim test; open field test

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