Dual action of exosomes derived from in vitro Aβ toxicity model: The role of age for pathological response

Beker M., Gunay N., Sarikamis B., Cakmak R. K., Ercin N., Altintas M. O., ...More

Archives of Gerontology and Geriatrics, vol.106, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 106
  • Publication Date: 2023
  • Doi Number: 10.1016/j.archger.2022.104874
  • Journal Name: Archives of Gerontology and Geriatrics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, ASSIA, Abstracts in Social Gerontology, BIOSIS, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Psycinfo, Veterinary Science Database
  • Keywords: Amyloid ?, Exosome, Hippocampus, Neurogenesis, Survival
  • Istanbul Medipol University Affiliated: Yes


Exosomes released from different cell types of the central nervous system play an essential role in the pathogenesis 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 Aβ 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 Aβ-exosomes. Interestingly, young animals represented increased numbers of neurons in the hippocampus, and neurogenesis was found to be restricted after Aβ-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 Aβ in both young and old animals. The findings reveal that the exosomes from an in vitro Aβ 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.