Therapeutic effects of melatonin-treated bone marrow mesenchymal stem cells (BMSC) in a rat model of Alzheimer's disease.

The therapy based on mesenchymal stem cells(MSCs) has received growing attraction for Alzheimer's disease(AD). However, a great challenge in this regard is the low survival rate of MSCs following transplantation. This study seeks to improve the therapy based on Bone Marrow MSCs (BM-MSCs) through melatonin (MT) pre-treatment, which is 'a known antioxidant' in an animal model of AD. In this paper, we separated BMSCs from the rat tibia and femur bones and then pretreated cells were with 5μM of MT for 24 h.The sample consisted of 40 male Wistar rats randomly assigned to the control, sham,MT-pretreated BMSCs and amyloid-beta (Aβ) peptide BMSCs groups.Two months after the cell transplantation,a number of tests including novel object recognition, Morris water maze, passive avoidance test, and open field test were undertaken. 69 days after the cell therapy,the rats were sacrificed.We removed brain tissues histopathological analysis and carried out immunohistochemistry for Beta tubulin, GFAP and iba1 proteins.The results suggested that both MT-BMSCs and BMSCs moved to brain tissues following the intravenous transplantation.However,MT-BMSCs had a significant effect on boosting learning, cognition and memory in comparison with BMSCs (P < 0.05). Furthermore, there was a significant rise in GFAP and Beta tubulin and substantial fall in microglial cells in the BMSCs in comparison with MT-BMSCs.Stem cell therapy has been proposed as an effective strategy for neurodegenerative diseases,but its therapeutic features are restricted.It has been shown that the pretreatment of MSCs with melatonin partly would boost cells efficiency and thereby alleviate AD complications such as memory and cognition.