<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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2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12356 |
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| author | Aleksandr V. Zhuravlev Polina N. Ivanova Ksenia A. Makaveeva Gennadii A. Zakharov Ekaterina A. Nikitina Elena V. Savvateeva-Popova |
| author_facet | Aleksandr V. Zhuravlev Polina N. Ivanova Ksenia A. Makaveeva Gennadii A. Zakharov Ekaterina A. Nikitina Elena V. Savvateeva-Popova |
| author_sort | Aleksandr V. Zhuravlev |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:36:13Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2c9c48e0f08f4d11bb4cefc9e67bc7872023-12-03T14:47:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201235610.3390/ijms232012356<i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term MemoryAleksandr V. Zhuravlev0Polina N. Ivanova1Ksenia A. Makaveeva2Gennadii A. Zakharov3Ekaterina A. Nikitina4Elena V. Savvateeva-Popova5Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, RussiaFaculty of Biology, Herzen State Pedagogical University of Russia, 191186 Saint Petersburg, RussiaEPAM Systems Inc., 41 University Drive, Suite 202, Newtown, PA 18940, USAPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, RussiaBeing 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.https://www.mdpi.com/1422-0067/23/20/12356<i>Drosophila</i><i>cardinal</i>3-hydroxykynureninephenoxazinone synthasecourtship suppressionlong-term memory |
| spellingShingle | Aleksandr V. Zhuravlev Polina N. Ivanova Ksenia A. Makaveeva Gennadii A. Zakharov Ekaterina A. Nikitina Elena V. Savvateeva-Popova <i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory International Journal of Molecular Sciences <i>Drosophila</i> <i>cardinal</i> 3-hydroxykynurenine phenoxazinone synthase courtship suppression long-term memory |
| title | <i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory |
| title_full | <i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory |
| title_fullStr | <i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory |
| title_full_unstemmed | <i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory |
| title_short | <i>cd</i><sup>1</sup> Mutation in <i>Drosophila</i> Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory |
| title_sort | i cd i sup 1 sup mutation in i drosophila i affects phenoxazinone synthase catalytic site and impairs long term memory |
| topic | <i>Drosophila</i> <i>cardinal</i> 3-hydroxykynurenine phenoxazinone synthase courtship suppression long-term memory |
| url | https://www.mdpi.com/1422-0067/23/20/12356 |
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