ZEBRAFISH AS A BEHAVIOR TEST MODEL FOR ANALYZING LEARNING/MEMORY ABILITY

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Dementia is a broad category of brain diseases. As the disease advances, symptoms include memory loss, movement disorders, problems with language, disorientation, mood swings and selfcare incapability. A platform for speedy screening of drugs/chemicals that cure or delay dementia is highly desirable. A behavior test for learning/memory ability was established by using a zebrafish neurodegenerative mutant. To establish the platform, an insertional mutant designated as DEGx was used. The allele showed a loss-of-function phenotype of DEGx as its transcript was not detected and its defects can be partially rescued by mRNA injection and phenocopied by morpholino knockdown experiments. The dysfunction of DEGx causes embryonic lethality and also neurodegenerative-like phenotypes shown by crossing to different neurally-related transgenic backgrounds. Additionally, an increase of hyperphosphorylated Tau was detected in the heterozygous adult males. For behavior analysis of heterozygous and WT adults, we established a platform that is based on reward training. There are three stages for the analysis. In the first stage, fish are trained to find food in the water T-maze and the time of finding food are recorded. The food-finding time of WT was decreased with daily training and shorter than that of heterozygotes. In the second stage, memory test is performed to examine whether the fish will swim to the goal arm where the food used to be. WT swam around the goal arm. In contrast, heterozygotes swam back and forth between arms. In the final stage, the cue card is swapped to check their linked memory ability. WT chose and also swam around the blue arm. In contrast, heterozygotes swam back and forth between blue and red arms, showing that they did not link blue card to food. Therefore, we demonstrated that wild-type adults have better abilities in learning, memory and linked memory. The behavioral abnormality of this insertional mutant is likely due to the neural defects depicted above. On one hand, we would like to dissect its underlining mechanism; on the other hand, the fish can be used to screen for drugs/chemicals with neuroprotective and/or anti-aging effect.