Long-term treatment with calcitriol (1,25(OH)2 vit D3) retards a biomarker of hippocampal aging in rats

Based on a literature implicating altered calcium homeostasis in brain aging and Alzheimer's Disease (AD) and evidence of decreased vitamin D action in AD subjects, the possibility was tested that calcitriol (1,25(OH)(2) vitamin D-3), the active form of vitamin D-3, might reduce markers of brain aging in rats. Animals were treated 5x weekly for prolonged periods (6-12 months) with either calcitriol in doses sufficient to elevate serum calcium and phosphate (20 ng/rat), calcitonin (1.5 IU/rat) or vehicle, in three separate long-term experiments on aging rats. New stereological methods (physical disector) of cell counting were used to evaluate neuronal density, a reliable biomarker of hippocampal aging in rats. In two experiments utilizing Brown-Norway x F344 hybrid rats (BN x F344), 8 months and 12 months of chronic treatment with calcitriol resulted in a higher density of CAI neurons in the middle regions of the hippocampus, compared to vehicle or calcitonin treatment. However, one study with aging F344 rats was terminated early because of extensive strain-specific pathology and no effect of calcitriol on neuronal density was observed. These studies suggest that, under some conditions, hormonal treatments that regulate calcium homeostasis can modulate markers of brain aging. (C) 1998 Elsevier Science Inc.