Hadeer Ahmed Mohamed Ibrahim - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
Abdelaziz Mohamed Hussein - Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Mahmoud Gabr - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
Rasha Aly El-Saeed - Division of Biochemistry, Chemistry Department, Faculty of Sciences, Mansoura University, Mansoura, Egypt.
Omar Abd-Alhakem Ammar - Basic Science Department, Delta University for Sciences and Technology, Gamasa, Egypt.
Ahmed Abdulatif Hassan Mosa - Department of Neurology, Faculty of Medicine, Delta University for Sciences and Technology, Gamasa, Egypt.
Abdel-Aziz Fatouh Abdel-Aziz - Division of Biochemistry, Chemistry Department, Faculty of Sciences, Mansoura University, Mansoura, Egypt.

Background: The current work investigated the effect of melatonin on differentiation of adipose mesenchymal stem cells (AD-MSCs) into dopamine producing cells and its effect on autophagy process and alpha-Synuclein (α-Syn) secretion.  Methods: AD-MSCs were characterized by flow cytometry and divided into ۴ groups; i) control group (AD-MSCs without any treatment), ii) M+MSCs group (MSCs treated with ۱ µM melatonin for ۱۲ days), iii) DN group (MSCs cultured in neurobasal A medium and essential neuronal growth factors for ۱۲ days) and iv) DN+M group (MSCs cultured in neurobasal A medium and ۱µM melatonin for ۱۲ days. By the end of experiments, the dopamine and α-Syn levels using ELISA, the expression of MAP-۲, m-TOR and α-Syn genes at the level of mRNA and detection of autophagosomes formation using transmission electron microscope were performed.  Results: We found that the isolated cells were MSCs due to their positivity expression for CD۱۰۵ and CD۹۰ and negativity expression for CD۳۴ and CD۴۵. The concentration of dopamine was significantly higher and α-Syn concentration was significantly lower in DN+M group when compared to other groups (P< ۰.۰۰۵). Also, this group showed the highly expression for MAP-۲ gene and less expression for m-TOR and α-Syn genes (P< ۰.۰۰۵). Moreover, there was significantly increase in autophagosomes formation in this group than another group (P< ۰.۰۰۵).  Conclusions: It is concluded that the melatonin promotes the differentiation of rat AD-MSCs into dopaminergic cells via induction of autophagy process and reduction of α-Syn secretion.

Alpha synuclein, Autophagy, Dopaminergic cells, Melatonin, Mesenchymal stem cells.