Age- related structural changes in the cerebellar cortex of the albino rats and the possible protective role of melatonin

ABSTRACT

It was reported that the cerebellum undergoes extensive atrophic changes with advanced age. The free radicals derived species are considered to be highly responsible for the aging process. Recently, melatonin was found to be a potent free radical scavenger. The aim of the current work was to demonstrate the age- related alterations in the structure of the cerebellar cortex in rals and 10 study the possible beneficial role of long - term melatonin administration to ameliorate these changes. In this work, a total number of 40 male albino rats were used, They were equally divided into 4 groups. Group I [young adult rats], it included 3-month- old rats. Croup II [middle -aged rats], it included 12- month - old rats. Group III [control old rats], it included 22- month- old rats. Group IV [melatonin- treated old rats], the animals of this group were treated with melatonin in a dose equal to 1mg/kg/day subcutaneously for 10 months. Their treatment began when they were 12 months old [middle -aged] and continued until they became 22 months old. At the end of the experiment the animals were sacrificed, and their cerebella were processed for light and transmission electron microscopic studies. In addition, the thickness of the molecular layer and the number of thepurkinje cells and granule cells per area [1800 um[2]] in their corresponding layers were measured in all the studied groups and statistically analyzed. The organization of the cerebellar cortex in the middle- aged rat group appeared to he closely similar to that of the young adult rats. In the old control rat group, examination of the cerebellar cortex revealed the presence of degenerative changes affecting the purkinje and the granule cells. These changes were associated with extensive cell loss. Marked decrease in the extent and branching of the dendrites of the purkinje cells could also be observed. In addition, there 'was a significant reduction in the thickness of the molecular layer. The old rat group treated with melatonin showed that the majority of the purkinje and granule cells had normal appearance. Only few cells had darkly stained nuclei. Furthermore, melatonin administration to the old rats markedly reduced aging- induced cell loss in the cerebellar cortex. The purkinje cells appeared to have many dendritic branches but still their extent was not reaching to the I'ial surface. The presynaptic nerve fiber terminals making contact with the granule cells and their dendrites showed the presence of considerable amount of synaptic vesicles. This study suggested that melatonin might have a potential role for attenuation of the age -related changes in the structure of the cerebellar cortex. It would he considered as a promising prophylactic or therapeutic agent for age -related neurological disorders