title: Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice.
abstract: L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice.
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary.
authors.forename: Dániel
authors.initials: D
authors.lastname: Varga
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Herédi
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Kánvási
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary ; Department of Neurology, Faculty of Medicine, MTA-SZTE Neuroscience Research Group, University of Szeged Szeged, Hungary.
authors.forename: Marian
authors.initials: M
authors.lastname: Ruszka
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kis
authors.affiliation: Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan ; Center of Biomedical Research, Research Center for Human Disease Modeling, Department of Physiological Sciences, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ono
authors.affiliation: Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan ; Center of Biomedical Research, Research Center for Human Disease Modeling, Department of Physiological Sciences, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Iwamori
authors.affiliation: Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan ; Center of Biomedical Research, Research Center for Human Disease Modeling, Department of Physiological Sciences, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Tokuko
authors.initials: T
authors.lastname: Iwamori
authors.affiliation: Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama Kita, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takakuwa
authors.affiliation: Department of Neurology, Faculty of Medicine, MTA-SZTE Neuroscience Research Group, University of Szeged Szeged, Hungary ; Department of Neurology, University of Szeged, Hungary Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary ; Department of Neurology, Faculty of Medicine, MTA-SZTE Neuroscience Research Group, University of Szeged Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Toldi
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged Szeged, Hungary ; Department of Neurology, Faculty of Medicine, MTA-SZTE Neuroscience Research Group, University of Szeged Szeged, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Gellért
keywords: C57Bl/6 mice; L-Kynurenine; anxiety; c-Fos; hippocampus; novel object recognition; open field; striatum