Protective effect of testosterone on cognitive deficits induced by ethidium bromide in experimental model of multiple sclerosis

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). The hippocampus is a vital center for learning and memory; it is extremely vulnerable to neurodegenerative diseases. The male hormones could be neuroprotective for the CNS. The current study is an attempt to investigate the effect of testosterone on learning and spatial memory following the demyelination of CA1 area by the injection of ethidium bromide in the rat's hippocampus. This experimental study has been conducted on healthy rats in the faculty of science of the Urmia University from September 2013 to February 2015. For demyelination in all previously gonadectomized healthy rats, 3µl ethidium bromide was injected into the CA1 area of rats by stereotaxic surgery. In addition, the treatment groups received 1µl testosterone (6µg/µl) during a 20-day timeframe on a daily basis after demyelination by the ethidium bromide. The control groups had no drug injection. The process of the learning and spatial memory of the rats were closely monitored by the radial Maze. The demyelination and remyelination in the hippocampus were checked by the myelin-specific coloring (Luxol fast blue and Cresyl violet). The histological results suggest that the testosterone is capable of minimizing the destructive impacts of ethidium bromide in the treatment group as well as enhancing the remyelination process. In the group treated by testosterone, the percentage of the pyknotic cells 20 days after demyelination induction, represented a significant reduction compared to that of ethidium bromide group (P=0.008). The behavioral studies analyses show that the amount of the food finding time in those groups received ethidium bromide was significantly longer than those of the control groups (P=0.001). Furthermore, the application of the testosterone in the treatment groups reduced the extent of demyelination while the memory impairment induced by the ethidium bromide was significantly improved (P=0.001). Testosterone can act as a neuroprotective factor that reduces the extent of demyelination and the number of pyknotic cells. It also may improve the learning and memory impairment induced by ethidium bromide.