The Effect of Systemic Administration of dbcAMP on Neural Stem Cells Migration in EAE Model of Multiple Sclerosis

Background and Novel strategies of MS try to stimulate endogenous neural stem cells for demyelination repair. Increased levels of cAMP potentiate the repair mechanisms in CNS by activating PKA or independently. In the present study، we investigated the effect of dbcAMP on neural stem cells migration in experimental autoimmune encephalomyelitis (EAE) model of MS. Methods and Materials: Mice were immunized with 300 µg MOG peptide emulsified in complete Freund''s adjuvant (CFA) and pertussis toxin (PT). Control mice received CFA and PT. Groups of EAE- mice received i. p. injections of dbcAMP 10mg/kg from day 9-14 or 9-21. Animals were observed daily for neurological deficit. Nestin expression was used as a marker to detect neural stem cells. The number of Nestin+ cells in SVZ and olfactory bulb (OB) was evaluated using immunohistochemical staining. GraphPad Prism Version 5 was used for analyzing the data. For the clinical signs of EAE، the differences between the same days were compared by unpaired t-test. For the number of Nestin+ cells، the statistical differences between the groups were determined by one-way ANOVA and Tukey post-test. EAE induction caused clinical signs and paralysis of tail and hind limbs. dbcAMP significantly reduced the incidence and severity of EAE in mice immunized with MOG. Maximum of scores reached 0. 66±0. 13 for dbcAMP treated mice (2. 5±0. 2 for EAE mice) on 21 dpi (day post inductin). EAE induction did not change number of nestin+ cells in SVZ but it increased it in OB. With developing of scores on 21dpi، the number of cells decreased (5. 66±1. 20). dbcAMP injection from 9-21 dpi increased these cells in SVZ. With developing of EAE scores on 21 dpi، the number of these cells in OB increased (19. 5±2. 04) and has significant differences with the control group. The treatment of EAE induced mice with dbcAMP from 9-21 dpi was assosiated with a significant elevation of Nestin+ cells in OB (40±2. 73) (P<0. 001). Treatment with the dbcAMP and PKA activation effectively control the EAE signs via increasing the number of neural stem cells and inducing their migration from SVZ to OB and demyelinated lesions، and decrease the symptoms.