Neural Stem Cell-conditioned Medium Protected Against Cognitive Dysfunction in APP/PS1 Mice

More and more evidence suggested neural stem cell conditioned medium (NSC-CM) exhibited a protective effect on regenerative medicine. Our previous studies suggested that NSC-CM ameliorated Aβ2-35-induced SH-SY5Y cell apoptosis as the cell model of Alzheimer's disease (AD). Thus, we hypothesized that NSC-CM had the capacity of neuro-protecting against cognitive dysfunction in APP/PS1 mice. Male APP/PS1 mice aged 6 months as the animal model of AD were randomly assigned into two groups: the control group and NSC-CM treated group. A 100 μl NSC-CM or PBS (phosphate-buffered saline) was administered slowly by tail vein once a day for consecutive 7 days or 14 days. The new object recognition test (NORT) and open field test (OFT) were applied to test cognition and emotion. The levels of phosphorylated tau (p-Tau), NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) were measured by Western blot. The load of amyloid-β (Aβ) plaque was measured by thioflavin S staining while the expression of astrocytes was observed by immunofluorescence staining. NSC-CM not only significantly ameliorated cognitive and emotional dysfunctions of APP/PS1 transgenic mice but also reduced the Aβ plaque load as well as the level of p-Tau, accompanied by increased astrocyte phagocytosis and inhibiting the inflammatory activation of astrocytes as well as the levels of NLRP3, caspase-1, and IL-1β. NSC-CM might be the alternative and promising therapeutic intervention for treating AD.