Mesenchymal stem cell-derived exosomes modulate the COX-IV pathway via inhibition of amyloidogenesis and mitoprotection in sodium azide- Alzheimer model in rats

Alzheimer's disease (AZD) has emerged as a catastrophic world health concern in tandem with the phenomenon of worldwide aging. The purpose of this study was to examine the curative effects of bone marrow stem cell-derived exosomes (BMSCDEXO) to overcome sodium azide (NaN 3 )-induced AZD in a rat model. The animals were classified into two main groups: the first group (8 rats) was kept as a control; the second group (24 rats) received intraperitoneal treatment with NaN 3 (12.5 mg/kg for the first five days and 10 mg/kg for the next nine days). Morris Water Maze (MWM) and Y maze tests were carried out to evaluate the Alzheimer's disease induction. Then, the animals were classified into three equal subgroups as follows: the AZD group, the AZD+ donepezil (DNP) group, in which animals orally received 5 mg/kg of DNP daily for four weeks, and the AZD+ BMSCDEXO group, in which animals were injected with a single dose of BMSCDEXO (intravenously, 100 µL). The results indicated that BMSCDEXO attenuated the behavioral signs in MWM and Y maze in the AZD group, which correlated with improvements in amyloid-beta precursor protein (AβPP), amyloid beta (Aβ) accumulation, and tau protein phosphorylation through mechanisms that involved the prevention of stress-related biochemical redox. Furthermore, it enhances the levels of antioxidant activities, mitochondrial functions, and cytochrome c oxidase (COX-IV ). Finally, we conclude that BMSCDEXO modulates cognitive impairment through inhibition of amyloidogenesis and mitoprotection in NaN 3 -induced AZD in comparison with the therapeutic drug donepezil.