Neural Stem Cells Secretome Increased Neurogenesis and Behavioral Performance and the Activation of Wnt/ β-Catenin Signaling Pathway in Mouse Model of Alzheimer’s Disease

In this study, mice were randomly allocated into three different groups as follows: Control, AD + Vehicle, and AD + NSCs-CM groups. To induce mouse model of AD, A β1-42 was injected into intracerebroventricular region. Following AD-like confirmation through thioflavin S staining and Passive avoidance test, about 5 µl mouse NSCs-CM was injected into the target areas 21 days after AD induction. For evaluation of endogenous proliferation rate (BrdU/Nestin+ cells), 50  µg/kbW BrdU was intraperitoneally injected for 5 consecutive days. To track NSC differentiation, percent of BrdU/NeuN+ cells were monitored via immunofluorescence staining. Histological Nissl staining was done to neurotoxicity and cell death in AD mice after NSCs-CM injection. Morris Water maze test was performed to assess learning and memory performance. Data showed that NSCs-CM could reverse the learning and memory deficits associated with A β pathology. The reduced expression of Wnt/β-catenin-related genes such asPI3K,Akt,MAPK, andERK in AD mice was increased. Along with these changes, NSCs-CM suppressed overactivity ofGSK3 β activity induced by A β deposition. Besides, NSCs increased BrdU/Nestin+ and BrdU/NeuN+ cells in a paracrine manner, indicating proliferation and neural differentiation of NSCs. Moreover, neurotoxicity rate and cell loss were deceased after NSCs-CM injection. In summary, NSCs can regulate adult neurogenesis through modulating of Wnt/ β-catenin signaling pathway and enhanc...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research