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

Objective: To investigate the effects of melatonin on neural stemcells and astrocytes in adult rats, and their relationships with learning and memory.Methods: Healthy adult Sprague-Dawley rats were randomly divided into thefollowing groups: sham, pinealectomized+vehicle, pinealectomized+melatoninreplacement(20ug/kg , 200ug/kg and 2mg/kg, ip). The number of proliferating cellnuclear antigen immunoreactive (PCNA-IR) cells in the subventricular zone(SVZ)of lateral ventricle and in the subgranular zone (SGZ) of dentate gyrus was counted ;and the number of glial acidic protein immunoreactive (GFAP-IR) cells inhippocampus, basal forebrain, caudate nucleus-putamen and anterior cingulatecortex was also counted. Learning and Spatial memory were tested in Morris watermaze. Results: The number of PCNA-IR cells in SVZ and SGZ, and the numberof GFAP-IR cells in hippocampus and basal forebrain were significantly decreasedin pinealectomized+vehicle group(P<0.01), while the above two parameters weresignificantly increased in pinealectomized+melatonin replacement (20ug/kg or200ug/kg) groups (P<0.01), which nearly reached the levels of sham group. Thechanges in the learning and memory in the same groups were similar to those in theabove parameters. However, a dose of melatonin replacement (2mg/kg) decreasedthe above parameters which reached the levels of pinealectomized+vehiclegroup.Whether pinealectomy or melatonin replacement was performed, the numberof GFAP-IR cells in caudate nucleus-putamen and anterior cingulate cortex was notsignificantly changed (p>0.05). Conclusion: Two doses of melatonin replacement(20ug/kg , 200ug/kg) for pinealectomized rats can increase the proliferation rate ofneural stem cells in SVZ and SGZ, and of astrocytes in hippocampus and basalforebrain with a greater ability of learning and spatial memory. The mechanism ofstrengthening learning and memory may involve the processes of melatoninreceptor-mediated signal transduction in neural stem cell and astrocytes. But greaterdose of melatonin replacement can supress the proliferation of neural stem cells andastrocytes with weakening learning and memory. These datas are valuable inclarification of neuroendocrine mechanism and in application of endogenous neuralstem cells for treating Alzheimer's disease.