Distinct Effects of The Hippocampal Transplantation of Neural And Mesenchymal Stem Cell In a Transgenic Model of Alzheimer’s Disease

Abstract Alzheimer’s disease (AD) is a highly disabling condition, with no cure currently available that accounts for 60-70% of all dementia cases worldwide. Therefore, the study of possible therapeutic strategies for AD is required. For that, animal models which resemble the main aspects of AD has been largely employed. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice presents amyloid-β (Αβ) plaques in the cortex and hippocampus, hyperlocomotion, cognitive deficits, and exacerbated inflammatory response. Recent studies showed that these neuropathological features were reversed by the transplantation of stem cells. However, the comparison of the effects induced by neural (NSC) or mesenchymal (MSC) stem cells was never investigated in an AD animal model before. In view of that, the present study aimed to evaluate whether NSC or MSC transplantation into the hippocampus of APP/PS1 mice reverse AD-related alterations, namely locomotor activity (open field test), short- and long-term memory (object recognition test), Αβ plaques formation (6-E10 immune staining) and microglia activation (Iba-1 immune staining) in the hippocampus. NSC and MSC engraftment reduced the number of hippocampal Αβ plaques in the hippocampus of APP/PS1 mice, and NSC reverted the peripheral hyperlocomotion activity displayed by APP/PS1 mice. Surprisingly, NSC increased microglia activation in the hippocampus of APP/PS1 mice and no impairment in short or long-term memory was observed in APP/PS1 mice. Altogether, this study reinforces the possible beneficial effects of NSC or MSC transplantation in the AD treatment.