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Singgih, Euginia L.; van der Voet, Monique; Schimmel-Naber, Marlies; Brinkmann, Emma L.; Schenck, Annette; Franke, Barbara

Investigating cytosolic 5′-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr)

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  • Medientyp: E-Artikel
  • Titel: Investigating cytosolic 5′-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr)
  • Beteiligte: Singgih, Euginia L.; van der Voet, Monique; Schimmel-Naber, Marlies; Brinkmann, Emma L.; Schenck, Annette; Franke, Barbara
  • Erschienen: Springer Science and Business Media LLC, 2021
  • Erschienen in: Translational Psychiatry
  • Sprache: Englisch
  • DOI: 10.1038/s41398-020-01149-x
  • ISSN: 2158-3188
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Cytosolic 5′-nucleotidases II (cNT5-II) are an evolutionary conserved family of 5′-nucleotidases that catalyze the intracellular hydrolysis of nucleotides. In humans, the family is encoded by five genes, namely <jats:italic>NT5C2</jats:italic>, <jats:italic>NT5DC1</jats:italic>, <jats:italic>NT5DC2</jats:italic>, <jats:italic>NT5DC3</jats:italic>, and <jats:italic>NT5DC4</jats:italic>. While very little is known about the role of these genes in the nervous system, several of them have been associated with neuropsychiatric disorders. Here, we tested whether manipulating neuronal expression of cNT5-II orthologues affects neuropsychiatric disorders-related phenotypes in the model organism <jats:italic>Drosophila melanogaster</jats:italic>. We investigated the brain expression of <jats:italic>Drosophila</jats:italic> orthologues of cNT5-II family (<jats:italic>dNT5A</jats:italic>-<jats:italic>CG2277</jats:italic>, <jats:italic>dNT5B</jats:italic>-<jats:italic>CG32549</jats:italic>, and <jats:italic>dNT5C-CG1814</jats:italic>) using quantitative real-time polymerase chain reaction (qRT-PCR). Using the <jats:italic>UAS</jats:italic>/<jats:italic>Gal4</jats:italic> system, we also manipulated the expression of these genes specifically in neurons. The knockdown was subjected to neuropsychiatric disorder-relevant behavioral assays, namely light-off jump reflex habituation and locomotor activity, and sleep was measured. In addition, neuromuscular junction synaptic morphology was assessed. We found that <jats:italic>dNT5A</jats:italic>, <jats:italic>dNT5B</jats:italic>, and <jats:italic>dNT5C</jats:italic> were all expressed in the brain. <jats:italic>dNT5C</jats:italic> was particularly enriched in the brain, especially at pharate and adult stages. Pan-neuronal knockdown of <jats:italic>dNT5A</jats:italic> and <jats:italic>dNT5C</jats:italic> showed impaired habituation learning. Knockdown of each of the genes also consistently led to mildly reduced activity and/or increased sleep. None of the knockdown models displayed significant alterations in synaptic morphology. In conclusion, in addition to genetic associations with psychiatric disorders in humans, altered expression of cNT5-II genes in the <jats:italic>Drosophila</jats:italic> nervous system plays a role in disease-relevant behaviors.</jats:p>
  • Zugangsstatus: Freier Zugang