Effect of Antioxidants on Medium-Term Memory Formation in Drosophila melanogaster cardinal Mutant

Никитина, Е. А.; Chernikova, Diana A.; Vasilyeva, O. V.; Журавлев, А. В.; Medvedeva, A. V.; Domnina, N.S.; Sergeeva, O.Yu.; Vol'eva, V.B.; Щеголев, Б. Ф.; Савватеева-Попова, Е. В.

doi:10.21519/0234-2758-2018-34-3-67-77

Cited by 5 publications

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“…On day 29, cd males demonstrate courtship song defects, such as high variance of interpulse interval (VIPI), while KYNA accumulation in cn seems to have neuroprotective effects, as their VIPI is lower compared to cd and the wild type Canton-S (CS; Savvateeva-Popova et al, 2003). For 5-day-old cd 1 , memory is impaired by heat shock and is restored by the application of a phenolic antioxidant (Nikitina et al, 2018). Heat shock induces apoptosis in cd 1 brain (Br) on day 5 (Savvateeva-Popova et al, 2003), which may be due to acceleration of 3-HOK autoxidation leading to hydrogen peroxide production.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…This makes cd , a Drosophila mutant with enzymatically disrupted XAN synthesis, a useful model to study specific effects of L-3HOK accumulation on neuropathology development [28]. 5-day-old cd male demonstrate a middle-term memory decrease after heat-shock–an effect prevented by adding phenolic antioxidants in the food media of developing flies [42]. Nowadays, there is a renaissance of interest in science to chemistry and physiology of ommochromes, the invertebrate pigments, including Drosophila brown pigments XAN and DXAN produced by L-3HOK dimerization, which also participate in many biological processes, such as electron transport and free radical trapping [43].…”

Section: Discussionmentioning

confidence: 99%

Enzymatic and non-enzymatic pathways of kynurenines' dimerization: the molecular factors for oxidative stress development

2018

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Kynurenines, the products of tryptophan oxidative degradation, are involved in multiple neuropathologies, such as Huntington's chorea, Parkinson's disease, senile dementia, etc. The major cause for hydroxykynurenines's neurotoxicity is the oxidative stress induced by the reactive oxygen species (ROS), the by-products of L-3-hydroxykynurenine (L-3HOK) and 3-hydroxyanthranilic acid (3HAA) oxidative self-dimerization. 2-aminophenol (2AP), a structural precursor of L-3HOK and 3HAA, undergoes the oxidative conjugation to form 2-aminophenoxazinone. There are several modes of 2AP dimerization, including both enzymatic and non-enzymatic stages. In this study, the free energies for 2AP, L-3HOK and 3HAA dimerization stages have been calculated at B3LYP/6-311G(d,p)//6-311+(O)+G(d) level, both in the gas phase and in heptane or water solution. For the intermediates, ionization potentials and electron affinities were calculated, as well as free energy and kinetics of molecular oxygen interaction with several non-enzymatically formed dimers. H-atom donating power of the intermediates increases upon the progress of the oxidation, making possible generation of hydroperoxyl radical or hydrogen peroxide from O2 at the last stages. Among the dimerization intermediates, 2-aminophenoxazinole derivatives have the lowest ionization potential and can reduce O2 to superoxide anion. The rate for O-H homolytic bond dissociation is significantly higher than that for C-H bond in non-enzymatic quinoneimine conjugate. However, the last reaction passes irreversibly, reducing O2 to hydroperoxyl radical. The inorganic ferrous iron and the heme group of Drosophila phenoxazinone synthase significantly reduce the energy cost of 2AP H-atom abstraction by O2. We have also shown experimentally that total antioxidant capacity decreases in Drosophila mutant cardinal with L-3HOK excess relative to the wild type Canton-S, and lipid peroxidation decreases in aged cardinal. Taken together, our data supports the conception of hydroxykynurenines' dual role in neurotoxicity: serving as antioxidants themselves, blocking lipid peroxidation by H-atom donation, they also can easily generate ROS upon dimerization, leading to the oxidative stress development.

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Effects of Weak Static Magnetic Field and Oligopeptides on Cell Proliferation and Cognitive Functions in Different Animal Species

et al. 2020

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Effect of Antioxidants on Medium-Term Memory Formation in Drosophila melanogaster cardinal Mutant

Cited by 5 publications

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

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

Enzymatic and non-enzymatic pathways of kynurenines' dimerization: the molecular factors for oxidative stress development

Effects of Weak Static Magnetic Field and Oligopeptides on Cell Proliferation and Cognitive Functions in Different Animal Species

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