AUTHOR=Zhuravlev Aleksandr V. , Vetrovoy Oleg V. , Ivanova Polina N. , Savvateeva-Popova Elena V. 

TITLE=3-Hydroxykynurenine in Regulation of Drosophila Behavior: The Novel Mechanisms for Cardinal Phenotype Manifestations

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00971

DOI=10.3389/fphys.2020.00971

ISSN=1664-042X

ABSTRACT=<p>Dysfunctions of kynurenine pathway of tryptophan metabolism (KPTM) are associated with multiple neuropathologies in vertebrates and invertebrates. <italic>Drosophila</italic> mutants with altered content of kynurenines are model objects for studying the molecular processes of neurodegeneration and senile dementia. The mutant <italic>cardinal</italic> (<italic>cd<sup>1</sup></italic>) with accumulation of the redox stress inductor 3-hydroxykynurenine (3-HOK) shows age-dependent impairments of the courtship song and middle-term memory. The molecular mechanisms for 3-HOK accumulation in <italic>cd<sup>1</sup></italic> are still unknown. Here, we have studied age-dependent differences in spontaneous locomotor activity (SLA) for the wild type strain <italic>Canton-S</italic> (<italic>CS</italic>), <italic>cd<sup>1</sup></italic>, and <italic>cinnabar</italic> (<italic>cn<sup>1</sup></italic>) with an excess of neuroprotective kynurenic acid (KYNA). We have also estimated the level and distribution of protein-bound 3-HOK (PB-3-HOK) in <italic>Drosophila</italic> brains (Br) and head tissues. The middle-age <italic>cd<sup>1</sup></italic> show the higher running speed and lower run frequency compared to <italic>CS</italic>, for <italic>cn<sup>1</sup></italic> the situation is the opposite. There is a decrease in the index of activity for 40-day-old <italic>cd<sup>1</sup></italic> that seems to be an effect of the oxidative stress development. Surprisingly, PB-3-HOK level in <italic>Drosophila</italic> heads, brains, and head capsules (HC) is several times lower for <italic>cd<sup>1</sup></italic> compared to <italic>CS</italic>. This complements the traditional hypothesis that <italic>cd<sup>1</sup></italic> phenotype results from a mutation in phenoxazinone synthase (PHS) gene governing the brown eye pigment xanthommatin synthesis. In addition to 3-HOK dimerization, <italic>cd<sup>1</sup></italic> mutation affects protein modification by 3-HOK. The accumulation of free 3-HOK in <italic>cd<sup>1</sup></italic> may result from the impairment of 3-HOK conjugation with some proteins of the brain and head tissues.</p>