The Effect of Caffeine on the Myelin Repair Following Experimental Demyelination Induction in the Adult Rat Hippocampus

Abstract

Multiple sclerosis is characterized by the loss of oligodendrocytes and demyelination of axons. In this study, the effect of caffeine on spatial memory in rats was investigated following demyelination induction by lysolecithin (LPC). The expression of Myelin Basic Protein (MBP), Glial Fibrillary Acidic Protein (GFAP), and Olig2 (oligodendrocyte lineage marker) genes was also assessed in the hippocampus. Animals were divided into seven groups; control group: animals received normal saline by stereotaxic intrahippocampal injection in Dentate Gyrus (DG) area; LPC group: animals received 2 μl lysolecithin by stereotaxic intrahippocampal injection in DG area (they were evaluated 7, 14, and 28 days after LPC injection; Caffeine- treated group: animals were treated with caffeine at doses of 30 mg/kg intraperitoneally for 7, 14, and 28 days after receiving LPC. Behavioral study was performed using Radial Arm Maze. Moreover, the RT- PCR was carried out for gene expression investigation. The demyelination and defective remyelination were noticeable on 28th day which suggests the demyelination decline caused by caffeine. Behavioral study showed that on the post-lesion days, the food finding time in the LPC group was significantly higher than that of the control group. Caffeine consumption significantly attenuated the food finding time in the treatment compared to the LPC group. The RT-PCR analysis indicated that the lysolecithin decreased the MBP expression especially on days 7 and 14 and conversely increased the Olig2 and GFAP expression. In addition, the caffeine enhanced the expression of MBP compared to that of the LPC group and reduced the Olig2 and GFAP expressions. Our results demonstrated that caffeine could increase the remyelination process in hippocampus and improve the spatial memory following demyelination induction by the LPC.