Dual action of exosomes derived from in vitro A beta toxicity model: The role of age for pathological response
Kalkan Çakmak, Rabia
Altıntaş, Mehmet Özgen
Beker, Mustafa Çağlar
Sarı Ak, Duygu
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CitationBeker, M., Günay, N., Sarıkamış, B., Kalkan Çakmak, R., Erçin, N., Altıntaş, M. Ö. ... Kılıç, Ü. (2023). Dual action of exosomes derived from in vitro A beta toxicity model: The role of age for pathological response. Archives of Gerontology and Geriatrics, 106. https://dx.doi.org/10.1016/j.archger.2022.104874
Exosomes released from different cell types of the central nervous system play an essential role in the patho-genesis of Alzheimer's disease (AD). In this study, we aimed to create an animal model by injecting exosomes that carry AD markers into the brain to shed light on the mechanism behind Alzheimer's pathology. Exosomes obtained from mouse Neuro2A, to which A beta toxicity model applied, were used as a mediator to build an AD phenotype. For this purpose, exosomes were administered into hippocampal CA3 region of mice with different ages. Firstly, the possible role of exosomes on brain volume was analyzed. Then, neurons and astrocytes were evaluated for survival. In addition, the progenitor cells' differentiation capacity was investigated via BrdU staining. AKT signaling pathway components were examined to detect the molecular mechanisms behind the exosomal function. We found different responses in different age groups. Expression of APP upregulated only in young animals upon delivery of A beta-exosomes. Interestingly, young animals represented increased numbers of neurons in the hippocampus, and neurogenesis was found to be restricted after A beta-Ex injections. However, in relation to exosome administration, the glial intensity increased in aged animals. Lastly, phosphorylation of survival kinase AKT was downregulated due to the presence of A beta in both young and old animals. The findings reveal that the exosomes from an in vitro A beta toxicity model may induce different responses in an age-dependent manner. This study is the first to report the relationship between exosomal function and aging by evaluating the key molecules.