Hydrogen sulfide and mesenchymal stem cells‐extracted microvesicles attenuate LPS‐induced Alzheimer's disease

Abstract Both hydrogen sulfide (H 2 S) and mesenchymal stem cells (MSCs) extracted microvesicles (MVs) are potent anti‐inflammatory molecules. They play an essential role in lowering the production of tumor necrosis factor‐alpha (TNF‐α). The latter could strongly stimulate MiR‐155 that contributes to neurodegeneration and Alzheimer's disease (AD). miR‐155 could repress the expression of inositol 5‐phosphatase‐1 (SHIP‐1) leading eventually to activation of Akt kinase and neurofibrillary development in AD. The current study was conducted to evaluate the role of miR‐155 in a rat model of lipopolysaccharide (LPS)‐induced AD and to investigate the effect of using MVs and H 2 S that were given either separately or combined in regulating pro‐inflammatory signaling. Thirty female Wistar albino rats aged 6 months to 1 year were equally divided into five groups; control group, LPS‐induced AD group, LPS + MVs group, LPS + NaHS group, and LPS + MVs and NaHS group. The increased miR‐155 level was associated with decreased SHIP‐1 level and positively correlated with TNF‐α. In addition, treatment with MVs and/or NaHS resulted in attenuation of inflammation, decreasing miR‐155, pAkt levels, and downregulation of apoptosis along with improvement of the hippocampal and cortical histopathological alterations. LPS enhanced production of malondialdehyde (MDA) and reduced glutathione (GSH) levels indicating oxidative stress‐induced neural damage, whereas MVs and NaHS could mitigate oxidative damage and accelerate antioxidant capacity via increasing catalase enzyme. In conclusion, downregulation of TNF‐α, miR‐155, and pAkt and increased SHIP‐1 could improve the neuro‐inflammatory state and cognitive function of LPS‐induced Alzheimer's disease.