Age-dependent changes in memory and mushroom bodies in the Drosophila mutant vermilion deficient in the kynurenine pathway of tryptophan metabolism.
Evolutionary conservation of homologous genes that cause related phenotypes in humans and Drosophila help to unravel genes implicated in polygenic human diseases. Among them are neurodegenerative disorders, such as Huntington, Parkinson, Alzheimer and HIV-induced diseases. They are characterized by a late onset disturbances of memory, changes in volumetric indices of the brain structures involved in memory formation, synaptic and glial pathology, and altered content of the intermediates of the kynurenine pathway, the endogenous modulators of the NMDA receptors. This pathway in conserved in insects, rodents and humans. We, therefore, studied the effects of aberrant tryptophan metabolism on memory, brain plasticity, synaptic and glial immunoreactivity in the Drosophila mutants vermilion (no kynurenines) and cinnabar (excess of neuroprotective kynurenic acid) over the life time. The mutant vermilion demonstrated gradual decline of 3-th memory performance and complete memory failure on the 28th day of life in a paradigm of conditioned courtship suppression. A drastic increase in the volume of the calyces of the mushroom bodies, and a decay in immunochemical staining of this brain structure with antibodies to synaptic protein csp and glia, precede the age-dependent memory defect and develop from the 12th day of adult life.
Savvateeva
E V
EV
Department of Psychiatry, University of Würzburg, Germany.
Popov
A V
AV
Kamyshev
N G
NG
Iliadi
K G
KG
Bragina
J V
JV
Heisenberg
M
M
Kornhuber
J
J
Riederer
P
P
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003214:Conditioning, Classical / Q000502:physiology; D004330:Drosophila; D007737:Kynurenine / Q000235:genetics / Q000378:metabolism*; D008568:Memory / Q000502:physiology*; D009154:Mutation; D012726:Sexual Behavior, Animal / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism*
D007737:Kynurenine; D014364:Tryptophan