| The pineal hormone melatonin not only regulates biological rhythms, but accumulating evidence suggests that it also acts as an antioxidant and stimulant of endogenous free radical scavenging systems. Melatonin levels decline with aging and even more so, in Alzheimer's disease. This experiment examined the effects of pinealectomy in the rat at different time points over a 20 month span using stereological neuron counts and neuropathological indices such as measures of cell death and markers of oxidative stress. Cognitive functioning was also assessed using the working memory version of the Morris water maze task and the elevated plus maze task. Since pinealectomy eliminates many neurohormones, some rats also received daily melatonin supplementation to determine if this would reverse the effects of pinealectomy. Animals were pinealectomized at 28 days of age and then were histologically examined at 2-month intervals up to 17 months of age. When tested at 2 months post surgery on the elevated plus maze, pinealectomized rats spent a greater proportion of time on the central hub compared to the sham rats. No other group differences were observed at this age nor were differences between the three groups found on any of this task's measures at 7 and 11 months post-surgery. At 15 months post-surgery, the melatonin-supplemented pinealectomized rats exhibited increased locomotor activity compared to the sham rats. Significant age effects were observed for all behavioral measures on the elevated plus maze task.; No significant impairment was observed on the morris water maze following 2, 7, or 11 months of pinealectomy. Age-related deficits in the Morris water maze were observed as 11-month rats performed more poorly than the 2-month rats. Pinealectomy caused a significant loss of hippocampal CAI pyramidal cells between 2 and 4 months following surgery. Loss of cells in the CA3 was evident at 2 months post-pinealectomy. Melatonin replacement in the drinking water prevented these effects of pinealectomy. The results indicated that melatonin not only sustains the viability of hippocampal pyramidal cells but remarkably, may even promote their genesis in the adult rat. (Abstract shortened by UMI.)... |
