Neurotoxic and neurobehavioral effects of kynurenines in adult insects.
Kynurenines are endogenous metabolites of tryptophan, which are studied extensively in vertebrates with respect to their etiological role in the pathology of various neurodegenerative disorders. In insects, metabolites of the kynurenic pathway are present in peak concentrations in the hemolymph of holometabolic species during pupation and just before eclosion. Unlike in larvae, these compounds cause severe motor dysfunction in adult species. Adult flesh flies were injected with various concentrations of these endogenous toxins and the effects on motor function were assessed. For tryptophan, L-kynurenine, 3-hydroxy-kynurenine, and anthranilic acid, the effects ranged from reversible to irreversible motor dysfunction, to instant paralysis and death. 3-Hydroxy-anthranilic acid could induce a tetanus like spasm of the wings. Tryptophan, 3-hydroxykynurenine, and 3-hydroxy-anthranilic acid were toxic to primary cultures of insect neurons. It is possible that some of these metabolites have a distinct role in larvae during the apoptotic events related to neurometamorphosis.
Cerstiaens
Anja
A
Laboratory of Developmental Physiology Genomics and Proteomics, K.U.Leuven, Naamsestraat 59, B-3000, Louvain, Belgium.
Huybrechts
Jurgen
J
Kotanen
Stephen
S
Lebeau
Ilya
I
Meylaers
Karen
K
De Loof
Arnold
A
Schoofs
Liliane
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004175:Diptera / Q000145:classification; D004305:Dose-Response Relationship, Drug; D006110:Grasshoppers / Q000145:classification; D007313:Insecta; D007737:Kynurenine / Q000633:toxicity*; D007928:Lethal Dose 50; D009420:Nervous System / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D017378:Quinolinic Acid / Q000633:toxicity*; D014364:Tryptophan / Q000633:toxicity*; D062367:ortho-Aminobenzoates / Q000633:toxicity*
D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid