Savvateeva E, Popov A, Kamyshev N, Bragina J, Heisenberg M, Senitz D, Kornhuber J, Riederer P
Department of Psychiatry, University of Würzburg, Federal Republic of Germany.
J Neural Transm (Vienna). 2000;107(5):581-601. doi: 10.1007/s007020070080.
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.
寻找具有与人类疾病相似表型的果蝇突变体，可能有助于揭示与多基因人类疾病相关的进化保守基因。其中包括神经退行性疾病，其特征为记忆出现迟发性障碍、突触和神经胶质病理变化、大脑结构损伤以及犬尿氨酸途径中间体含量改变，这些中间体是谷氨酸兴奋毒性和氧化毒性的调节剂。该途径在昆虫、啮齿动物和人类中是保守的。我们测试了果蝇突变体“红衣主教”（3 - 羟基犬尿氨酸过量）和“朱砂”（犬尿酸过量）在记忆、突触病理、大脑结构可塑性和神经胶质免疫反应性方面的年龄依赖性变化。在条件性求偶抑制范式中，突变体“红衣主教”在出生后第12天到第29天学习和记忆能力下降。记忆衰退伴随着对突触半胱氨酸串蛋白免疫反应性的急剧下降，以及蘑菇体体积参数的改变，蘑菇体是与记忆相关的大脑结构。
