<i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory

<i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory

Being involved in development of Huntington’s, Parkinson’s and Alzheimer’s diseases, kynurenine pathway (KP) of tryptophan metabolism plays a significant role in modulation of neuropathology. Accumulation of a prooxidant 3-hydroxykynurenine (3-HOK) leads to oxidative stress and neuronal cell apoptos...

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Bibliographic Details
Main Authors: Aleksandr V. Zhuravlev, Polina N. Ivanova, Ksenia A. Makaveeva, Gennadii A. Zakharov, Ekaterina A. Nikitina, Elena V. Savvateeva-Popova
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
<i>Drosophila</i>
<i>cardinal</i>
3-hydroxykynurenine
phenoxazinone synthase
courtship suppression
long-term memory
Online Access:https://www.mdpi.com/1422-0067/23/20/12356
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Summary:Being involved in development of Huntington’s, Parkinson’s and Alzheimer’s diseases, kynurenine pathway (KP) of tryptophan metabolism plays a significant role in modulation of neuropathology. Accumulation of a prooxidant 3-hydroxykynurenine (3-HOK) leads to oxidative stress and neuronal cell apoptosis. <i>Drosophila</i> mutant <i>cardinal</i> (<i>cd</i><sup>1</sup>) with 3-HOK excess shows age-dependent neurodegeneration and short-term memory impairments, thereby presenting a model for senile dementia. Although <i>cd</i> gene for phenoxazinone synthase (PHS) catalyzing 3-HOK dimerization has been presumed to harbor the <i>cd</i><sup>1</sup> mutation, its molecular nature remained obscure. Using next generation sequencing, we have shown that the <i>cd</i> gene in <i>cd</i><sup>1</sup> carries a long deletion leading to PHS active site destruction. Contrary to the wild type <i>Canton-S</i> (<i>CS</i>), <i>cd</i><sup>1</sup> males showed defective long-term memory (LTM) in conditioned courtship suppression paradigm (CCSP) at days 5–29 after eclosion. The number of dopaminergic neurons (DAN) regulating fly locomotor activity showed an age-dependent tendency to decrease in <i>cd</i><sup>1</sup> relative to <i>CS</i>. Thus, in accordance with the concept “from the gene to behavior” proclaimed by S. Benzer, we have shown that the aberrant PHS sequence in <i>cd</i><sup>1</sup> provokes drastic LTM impairments and DAN alterations.
ISSN:1661-6596
1422-0067

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