title: Effect of kynurenic acid on development and aging in wild type and vermilion mutants ofDrosophila melanogaster.
abstract: BACKGROUND
  Up-regulation of tryptophan (Trp) conversion into kynurenine (Kyn) and increased formation of down-stream metabolites of Kyn is one of the mechanisms of aging and neurodegenerative disorders. Kyn is an immediate precursor of kynurenic acid (KYNA), an antagonist to NMDA and α7nAChR receptors and activator of aryl hydrocarbon receptor. Increased formation of KYNA ameliorates neurodegeneration and eclosion defect in Drosophila model of Huntington's Disease.
  
  
  OBJECTIVE
  Effect of KYNA on pupae viability and life span was evaluated in wild type (Canton-S, CS) andvermilionDrosophila mutants with deficient formation of Kyn due to mutation ofvermiliongene (v) that encodes the Trp-2,3-dioxygenase (TDO), enzyme catalyzing Trp conversion into Kyn.
  
  
  METHODS
  Vermilion mutants were transferred into the Canton-S genetic background (v-CS). KYNA effect on viability (number of filial generation pupae and %% of their lethality) was assessed in pupae maintained at standard temperature (23°C). KYNA effect on life span was evaluated in adult (imago) flies maintained at 28°C (accelerated aging).
  
  
  RESULTS
  KYNA drastically increased (4 fold from 8.36 to 33.62) %% of dead pupae in Canton-S but not inv-CS flies (p=0.0001). KYNA did not affect life span of female Canton-S flies but decreased life span ofv-CS female flies (from 17.15 to 14.29 days). KYNA increased life span of male Canton-S (from 17.92 to 19.96 days) and v-CS flies (14.52 to 17.75 days).
  
  
  CONCLUSIONS
  This the first (to the best of our knowledge) observation of the toxic effect of KYNA in Drosophila pupae. KYNA effect on high-temperature induced aging acceleration was gender dependent. Present data support the role of downstream Kyn metabolites in aging mechanisms.
authors.affiliation: Department of Genetics and Cytology, V.N. Karazin Kharkiv National University, Ukraine.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Navrotskaya
authors.affiliation: Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University/Tufts Medical Center, Boston, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Oxenkrug
keywords: Drosophila melanogaster; aging; development; kynurenic acid; neurodegenerative disorders; vermilion