Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Memory Enhancement with Kynurenic Acid and its Mechanisms in Neurotransmission

Version 1 : Received: 20 March 2022 / Approved: 24 March 2022 / Online: 24 March 2022 (08:57:45 CET)

A peer-reviewed article of this Preprint also exists.

Martos, D.; Tuka, B.; Tanaka, M.; Vécsei, L.; Telegdy, G. Memory Enhancement with Kynurenic Acid and Its Mechanisms in Neurotransmission. Biomedicines 2022, 10, 849. Martos, D.; Tuka, B.; Tanaka, M.; Vécsei, L.; Telegdy, G. Memory Enhancement with Kynurenic Acid and Its Mechanisms in Neurotransmission. Biomedicines 2022, 10, 849.

Journal reference: Biomedicines 2022, 10, 849
DOI: 10.3390/biomedicines10040849

Abstract

Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed following 24 hours. High doses of KYNA (i.e., 20-40 μg/2 μl) significantly decreased the avoidance latency, whereas a low dose of KYNA (0.5 μg/2 μl) significantly elevated it compared with controls, suggesting that the low dose of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate systems in the nootropic effect. The study confirmed that a low dose of KYNA improved a memory component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.

Keywords

tryptophan; kynurenine; kynurenic acid; passive avoidance; cognitive domain; memory; cognitive enhancer; neurotransmission; receptor blockers; translational

Subject

MEDICINE & PHARMACOLOGY, Psychiatry & Mental Health studies

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