Zebra balığı (Danio rerio) model organizması kullanılarak yaşlanmanın beyindeki inflamatuar, hücre iskeleti, ve mikroglia belirteçlerindeki gen ifade düzeyleri üzerine etkileri

Age-related cognitive decline burdens the elderly population, limiting their ability to socialize and be independent. To be able to develop proper treatments, healthy aging should be examined. Previous studies focusing on healthy brain aging revealed that abnormal microglial activation was observed. Aging microglia exhibits 0partial loss of motility due to cytoskeletal changes, leading to decreases in their ability to respond to environmental cues. Thus, a more inflammatory phenotype was observed in microglia. These disruptions of the previously established homeostasis in the brain could be the underlying reason for cognitive decline experienced during aging. To understand these changes during aging in the brain, cytoskeletal, microglial, and inflammation-related markers were investigated by using both in silico and in vivo approaches. In silico analyses were performed on mice hippocampus and the whole brain revealed that the genes involved in the actin cytoskeleton reorganization (Arpc1b), neurogenesis (Erbb4), and proinflammatory related pathways (Il1b, P2x7r, Elf2b) showed differential gene expression levels among different age groups, genders, and tissue of origin. On the other hand, no differential expression was observed in microglial (Coro1a and Aif1) and anti-inflammatory markers (Tgfb1 and Il10). To further validate these results in vivo, quantitative polymerase chain reaction (qPCR) was performed on young and old zebrafish brains. According to the results, only two genes showed marginally significant differences among young and old brains: arpc1b and p2x7r. These results collectively could mean 1) the overall microglia population does not change during aging, 2) the brain does not exhibit imbalances in terms of pro- and anti-inflammatory cytokines, and 3) neurogenesis. Furthermore, the significant changes observed in arpc1b and p2x7r indicated the iii iv importance of the cytoskeleton and inflammation-related pathways in the correct functioning of the cells. Therefore, this study showed that in silico analysis are the reliable indicators of in vivo experiments, zebrafish can be used as a gerontological model, and the importance of cytoskeleton in motile cells. However, to understand these described relations, further investigation on the protein level of these genes should be done.