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 D3), the active form of vitamin D3, 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 CA1 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.
Landfield
P W
PW
Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536, USA. pwland@pop.uky.edu
Cadwallader-Neal
L
L
D000375:Aging / Q000502:physiology*; D000818:Animals; D002116:Calcitonin / Q000032:analysis / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002120:Calcium Channel Agonists / Q000378:metabolism / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000032:analysis / Q000097:blood; D002452:Cell Count; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014807:Vitamin D / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002130:Calcium Phosphates; D018696:Neuroprotective Agents; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D014807:Vitamin D; C485838:calcium phosphate, monobasic, anhydrous; D002116:Calcitonin; C020243:calcium phosphate; D002117:Calcitriol; C485829:calcium phosphate, dibasic, anhydrous; D002118:Calcium