Therapeutic Effects of Melatonin-Treated Bone Marrow Mesenchymal Stem Cells (BMSC) in a Rat Model of Alzheimer s Disease

Background and Aim : Mesenchymal stem cells based therapy has extensive attraction for Alzheimer’s disease (AD). However, low survival rate of MSCs after transplantation is a huge challenging. Objective: The current study aimed to improve Bone Marrow MSCs (BM-MSCs)-based therapy by their pre-treatment with melatonin (MT) ‘a well-known antioxidant’ in an animal model of AD.Methods : In this study, BMSCs from the rat tibia and femur bones was separate, the cells were pretreated with 5μM of MT for 24 hours. Forty male Wistar rats were randomly allocated to control, sham, amyloid-beta (Aβ) peptide BMSCs and MT-pretreated BMSCs groups. The novel object recognition, passive avoidance test, Morris water maze and open field test were performed two months following the cell transplantation. The rats were sacrificed 69 days following cell therapy. The brain tissues were removed for histopathological analysis and also immunohistochemistry was performed for GFAP, Beta tubulin and iba1 proteins.Results : It has been revealed that both BMSCs and MT-BMSCs migrated to brain tissues after intravenous transplantation. However, MT-BMSCs significantly improved learning, memory and cognition compared with BMSCs (P<0.05). Furthermore, increase GFAP and Beta tubulin and reduction of microglial cells were significantly increased in the BMSCs compared with MT-BMSCs.Conclusion : Although stem cell therapy has been introduced as a promising strategy in neurodegenerative diseases, however, its therapeutic properties are limited. It is suggested that pretreatment of MSCs with melatonin partly would increase the cells efficiency and consequently could decrease AD complication including memory and cognition.

Keywords:

Alzheimer’s disease , β-amyloid , Stem Cells , Melatonin