The Preliminary Study On The Impariment Of Memory In Zebrafish Induced By Aluminum And Its Mechanism

Alzheimer’s disease (Alzheimer’s disease, AD) is a kind of progressive neurodegenerative disease which is persistent characterized with memory impairment, cognitive dysfunction, abnormal behavior and personality changes.With the rapid increase of the world population aging, AD prevalence increased year by year, and its pathogenesis has not yet clear because of the complexity.Therefore the study of the pathogenesis of AD in depth has important implications to seek ways for the treatment and prevention of AD.Zebrafish as a new vertebrate model is widely used in studies of human neurological diseases, because their brain tissues such as the olfactory bulb hypothalamus, cerebral cortex, central nervous system and the major neurotransmitter systems such as cholinergic, dopaminergic, noradrenergic pathways are similar to that of mammals;moreover, its embryo and larval are small, transparent, develop rapidly and easy to be real-time observed and adult zebrafish are small, spawn large amount, easy-to high-throughput screening, etc.Al hypothesis is one of the AD pathogenesis, and Al is a neurotoxin but no biological role.It can induce oxidative damage which lead to neuronal death, but also promote the formation of senile plaques and neurofibrillary tangles.Therefore, it can result in pharmacology and behavioral changes which can be seen in Alzheimer’s disease.The mechanism of Al toxicity has not yet been defined because its complexity.Therefore, the mechanisms of the impariment of memory in zebrafish induced by aluminum are explored by behavioral and genetic method:After6-8month old adult zebrafish (AB) was soaked in AICl3solution for30days, the learning and memory abilities was tested by T maze; then the biochemical parameters related neural activity and glucose metabolism was determined.Finally,In order to elaborate the molecular mechanisms of Al-induced learning and memory damage preliminary and objectively,abnormal expression of some genes were choosed by microarray analysis and reverse transcription quantitative PCR to examine the impact of A1toxicity on the signaling pathways and protein abnormalities comprehensively. The T-maze results:the latency in aluminum group to find the nutrition-rich chamber (EC) in the last training increased significantly compared with the first training (P<0.05), and the latency in control group to find the nutrition-rich chamber (EC) in the last training increased significantly compared with the first training (P<0.01). The biochemical parameters results:The biochemical parameters in aluminum group compared with the control group showed that AchE activity increased significantly, SOD activity decreased significantly (P<0.01),MDA content increased significantly (P<0.01), HK activity decreased significantly, PFK activity decreased significantly (P<0.01);and PK activity was not significantly different. Microarray and RT-qPCR analysis results:of the imediate early genes, compared with the control group, the expression of egr2b was up-regulated significally in aluminum group,and the expression of egr4, v-fos was up-regulated in aluminum group significantly;Of the genes which were related to sugar metabolism, pfkfb41mRNA transcript level was significantly reduced(P<0.01), but aldob mRNA transcript level had no significant differences; of the other genes which were related to the learning and memory, syt5,one of synaptotagmin genes,mRNA transcript level was significantly elevated(P<0.05), sl00al0b,one of calcium-binding protein genes,m RNA transcript level decreased significantly(P<0.01),icn,one of calcium-binding protein genes, mRNA level was significantly reduced(P<0.05),hsp90one of heat shock protein genes, mRNA transcript level was significantly reduced(P<0.01), and LOC569958,one of the S100A genes,mRNA transcript level had no significant difference. Conclusion:In this study, the Al-induced impact of memory in zebrafish and its related mechanisms of toxicity are explored with behavior and genetic methods, indicating that A1impaired the learning and memory by various mechanisms such as interfering with neurotransmitter release,reducing the level of glucose metabolism,inducing oxidative stress and cell death.lt provides an important theoretical basis to the mechanism of aluminum-induced Alzheimer’s disease.