Yaşlanan beyinde inflamasyon sürecinin etkisi: In vıtro ve ex vıvo modellerinden elde edilen kanıtlar

Aging is a complex and dynamic process that is characterized by a gradual decline over time in the physiological integrity of organisms. Several cellular mechanisms contribute to aging, including telomere shortening, damage accumulation in DNA, disabled macroautophagy, mitochondrial dysfunction, and cellular senescence. These processes, consecutively, lead to impaired cellular function, declined tissue repair, and stem cell exhaustion and are seen in the development of neurodegenerative disorders and healthy aging. One of the hallmarks of brain aging is the altered chronic inflammatory status of the brain. The over-activation and polarization of microglia, increased secretion of pro-inflammatory cytokines and reactive oxygen species, inflammasome activation, and the upregulation of the NF- κB signaling pathway are among the markers of neuroinflammation. This mechanism's anticipated effects include dysregulated nutrition sensing via the mTOR (mammalian target of rapamycin) pathway, decreased neurogenesis, and synaptic integrity over time. Another element that contributes to vulnerability to inflammation is genetic predisposition. Hence, additional research endeavors are required to investigate the influence of dietary interventions and therapeutic modalities targeting inflammation on genetic pathways. Thus, this study aimed to understand how inflammation can be triggered on different models, investigate potential inflammation-related biomarkers with meta-analysis and observe the effect of inflammation for both zebrafish primary brain cells and murine microglial cells. We conducted short-term copper sulfate treatments on both models for this objective. Moreover, to examine the effects of intermittent fasting, an mTOR downregulator, and high-fat diet, an inflammation inducer, on the brain of zebrafish at the molecular level by primary cell culture method. Finally, we applied rapamycin+DMSO treatment to primary cells to assess the possibility of reversing the progression of inflammation. The results showed that copper sulfate is an efficient oxidative stress-induced inflammatory reagent for zebrafish; however, it did not cause a direct inflammatory response in murine microglial cells. For zebrafish, in the copper sulfate+DMSO treated group, age affected Nrf2a mRNA, altering oxidative stress in old animals. Regardless of diet and treatment group, inflammation markers were higher in old animals, which underscores the association between aging and chronic inflammation. Elevated Lc3b levels in young and old animals captured that high copper concentrations can trigger autophagy. Results for neurogenesis markers revealed that overfeeding or acute inflammation could contribute to compromised neurogenesis in advanced stages of life. On the contrary, the enhanced neurogenesis potential of intermittent fasting in old animals was revealed. In conclusion, this study has demonstrated that the modulation of neuroinflammatory responses, as well as oxidative stress, neurogenesis, and autophagy, occurs in an age-related manner. Moreover, dietary or pharmaceutical interventions could yield comprehensive outcomes in perceiving the brain's neuroinflammatory profile during aging.