Age-dependent memory loss, synaptic pathology and altered brain plasticity in the Drosophila mutant cardinal accumulating 3-hydroxykynurenine.
A search for Drosophila mutants with phenotypes similar to human diseases might help to unravel evolutionary conserved genes implicated in polygenic human disorders. Among these are neurodegenerative diseases, characterized by a late onset disturbance of memory, synaptic and glial pathology, structural brain impairments and altered content of the intermediates of the kynurenine pathway, the modulators of glutamate excito- and oxidative toxicity. This pathway is conserved in insects, in rodents, and in humans. We tested the Drosophila mutants cardinal (3-hydroxykynurenine excess) and cinnabar (kynurenic acid excess) for age-dependent changes in memory, synaptic pathology, structural brain plasticity and glial immunoreactivity. The mutant cardinal demonstrated a decline in learning and memory from the 12th to the 29th day of life in a paradigm of conditioned courtship suppression. Memory decline was accompanied by a sharp decrease in immunoreactivity to the synaptic cysteine string protein, and alterations in volumetric parameters of the mushroom bodies, the brain structures implicated in memory.
Savvateeva
E
E
Department of Psychiatry, University of Würzburg, Federal Republic of Germany. sav@pavlov.infran.ru
Popov
A
A
Kamyshev
N
N
Bragina
J
J
Heisenberg
M
M
Senitz
D
D
Kornhuber
J
J
Riederer
P
P
D000367:Age Factors; D000818:Animals; D003380:Courtship; D004330:Drosophila; D007736:Kynurenic Acid / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D007858:Learning / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism
C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D007736:Kynurenic Acid