Evaluation of the effect of neuronal stem cells- Conditiend -Medium on neurognenesis, Wnt-β catenin signaling pathway and neurocognitive behaviors in Alzheimer’s disease model

Abstract

Alzheimer’s disease is a progressive age-related neurodegenerative disorder that affects a large number of people throughout the world. Studies have shown that neuronal stem cells have the ability to secrete neurotrophic factors, further, these factors have great potential of healing the damaged brain. This research studied the effect of neural stem cells- conditioned-medium on the Wnt-β Catenin pathway, neurogneis and behavioralperformance in a model of Alzheimer’s disease. Methods: In the present study, mice were divided into three groups: control group, AD+ PBS, and AD + Neural stem cells -Coditioned-Medium(NSCs-CM). To induce AD, Aβ 1-42 was injected into the lateral ventricles, and after 21 days, the shuttle box was used to confirm the Alzheimer’s model and cognitive impairment. Then PBS and conditioned- medium for treatment were injected in different groups. 50 µg/kbW BrdU was injected intraperitoneally for 5 continues days to evaluate cell proliferation. One month after the last dose of BrdU, spatial memory was assessed by the Morris water maze. The expression of BrdU / Nestin and BrdU / NeuN was studied by immunofluorescence to evaluate the proliferation and neurogenesis of neural stem cells in the hippocampus. In addition, cell death and neurotoxicity were assessed by Nissl staining and the expression of Wnt / β-catenin, PI3K, Akt, MAPK, ERK and GSK3β genes by real-time RT-PCR. Results: The results of this study showed that Aβ reduced spatial learning and memory. While treatment with NSCs-CM was able to increase the expression of increased the proliferation and neural differentiation of the neural stem cells in the hippocampus as well as the expression of Wnt / β-catenin, PI3K, Akt, MAPK, ERK genes, which indicates improved neurogenesis. In addition, GSK3β expression and cell death increased after injection of Aβ while NSCs-CM ameliorated these effects.