Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

Dániel Varga, Judit Herédi, Zita Kánvási, Marian Ruszka, Z. Kis, Etsuro Ono, Naoki Iwamori, Tokuko Iwamori, Hiroki Takakuwa, L. Vécsei, J. Toldi, Levente Gellért

Research output: Article

14 Citations (Scopus)

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.

Original languageEnglish
Article numberA157
JournalFrontiers in Behavioral Neuroscience
Volume9
Issue numberJune
DOIs
Publication statusPublished - jún. 16 2015

Fingerprint

Kynurenine
Sulfates
Kynurenic Acid
Proto-Oncogene Proteins c-fos
Hippocampal CA1 Region
Memory Disorders
Short-Term Memory
Synaptic Transmission
Tryptophan
Hippocampus
Anxiety
Recognition (Psychology)
Brain

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology

Cite this

Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice. / Varga, Dániel; Herédi, Judit; Kánvási, Zita; Ruszka, Marian; Kis, Z.; Ono, Etsuro; Iwamori, Naoki; Iwamori, Tokuko; Takakuwa, Hiroki; Vécsei, L.; Toldi, J.; Gellért, Levente.

In: Frontiers in Behavioral Neuroscience, Vol. 9, No. June, A157, 16.06.2015.

Research output: Article

Varga, Dániel ; Herédi, Judit ; Kánvási, Zita ; Ruszka, Marian ; Kis, Z. ; Ono, Etsuro ; Iwamori, Naoki ; Iwamori, Tokuko ; Takakuwa, Hiroki ; Vécsei, L. ; Toldi, J. ; Gellért, Levente. / Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice. In: Frontiers in Behavioral Neuroscience. 2015 ; Vol. 9, No. June.
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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.",
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AU - Kánvási, Zita

AU - Ruszka, Marian

AU - Kis, Z.

AU - Ono, Etsuro

AU - Iwamori, Naoki

AU - Iwamori, Tokuko

AU - Takakuwa, Hiroki

AU - Vécsei, L.

AU - Toldi, J.

AU - Gellért, Levente

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