Effects Of Melatonin On Brain Cells In Adult Hypertensive Rats: Implication Of Learning And Memory

Objective:To investigate the effects of melatonin on brain cells in adult hypertensive rats and their relationships with learning and memory. Methods:Healthy adult Wistar rats were randomly divided into three groups: sham,renovascular hypertensive,renovascular hypertensive plus melatonin-treated(20μg/kg,i.p).Learning and Spatial memory were detected in Morris water maze.Immunohistochemical analyses were made on bromodeoxyuriding(BrdU),ChAT-positive,GFAP-positive and NF-posivive cells,while double-immunohistochemical analyses on BrdU+GFAP- and BrdU+NF-positive cell.Results:The number of BrdU immunoreactive (BrdU-IR)cells in the subventricular zone(SVZ),the subgranular zone(SGZ) of dentate gyrus and rostral migratory stream(RMS),and the number of NF-positive cells in hippocampus and in cortex were significantly decreased in renovascular hypertensive group(P＜0.01).The number of ChAT-posibive cells in diagonal band of the basal forebrain and the number of BrdU+NF positive cell of olfactory bulb were decreased in renovascular hypertensive group, GFAP-positive cell and BrdU+ GFAP positive cells were increased significantly(P＜0.01).The changes in the performance of learning and memory among the three groups were similar to those in the above parameters.The change in the above parameters were significantly reversed by melatonin treatment group(P＜0.01),which nearly reached the levels of the normal control group.Conclusion:Melatonin treatment can increase the proliferation rate of neural stem cells in SVZ and SGZ,induce the neural stem cell in vitro to migrate and differentiate into more neurons than astrocytes in renovascular hypertensive rats.The melatonin also up-regulates the expressions of choline acetyltransferase and NF positive cells,which are parallelled to the performance of learning and spatial memory.These data imply that the improvements of melatonin in abilities of learning and memory of adult hypertensive rats may be closely related to the actions of melatonin on the neurogenesis and matured neurons.