Regulation of calcitonin secretion in normal man by changes of serum calcium within the physiologic range.

To examine the relative importance of calcium and gastrin in regulation of calcitonin secretion, we administered graded oral doses of calcium to 10 normal men, ages 23-29 yr. Each subject had previously shown an appropriate increase in calcitonin secretion in response to a pharmacologic (0.5 mug/kg) pentagastrin injection. On separate days and in random order, each man drank 250 ml of distilled water containing 0.0, 0.5, 1.5, and 3.0 g of elemental calcium as the gluconate salt. Blood samples were drawn before and at 30, 60, 90, 120, 180, and 240 min after the oral calcium dose. The samples were analyzed for calcium by atomic absorption spectroscopy, and for gastrin and calcitonin by radioimmunoassays of established sensitivity and specificity. Ingestion of water (control) caused no change in any of the three variables. Calcium ingestion resulted in dose-related increases, within the normal range, of all three variables. Immunoreactive gastrin rose promptly, peaking at 30 min, and returning to basal levels or below by 120 min. In contrast, calcium and immunoreactive calcitonin levels rose slowly and in parallel, peaking at 120-240 min. Changes in calcitonin and changes in calcium were strongly and positively correlated, r = 0.73, when all data were pooled. Furthermore, individual linear regressions for changes in calcitonin and calcium levels (calculated separately for the three oral calcium doses in each subject) had positive slopes in 28 out of 30 sets (P < 0.01). The changes in calcitonin concentrations were much more poorly correlated with the corresponding changes in serum gastrin levels; in fact, the regression coefficient was weakly negative, r = -0.20. These results show that, at least in young adult men, changes of ambient calcium concentration within the normal range may be of major importance in physiologic regulation of calcitonin secretion. The findings are consistent with the hypothesis that calcitonin functions to prevent excessive postprandial hypercalcemia.

Behavioral assessment of Alzheimer's transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory.

Long-term vaccinations with human beta-amyloid peptide 1-42 (Abeta1-42) have recently been shown to prevent or markedly reduce Abeta deposition in the PDAPP transgenic model of Alzheimer's disease (AD). Using a similar protocol to vaccinate 7.5-month-old APP (Tg2576) and APP+PS1 transgenic mice over an 8-month period, we previously reported modest reductions in brain Abeta deposition at 16 months. In these same mice, Abeta vaccinations had no deleterious behavioral effects and, in fact, benefited the mice by providing partial protection from age-related deficits in spatial working memory in the radial arm water maze task (RAWM) at 15.5 months. By contrast, control-vaccinated transgenic mice exhibited impaired performance throughout the entire RAWM test period at 15.5 months. The present study expands on our initial report by presenting additional behavioral results following long-term Abeta vaccination, as well as correlational analyses between cognitive performance and Abeta deposition in vaccinated animals. We report that 8 months of Abeta vaccinations did not reverse an early-onset balance beam impairment in transgenic mice. Additionally, in Y-maze testing at 16 months, all mice showed comparable spontaneous alternation irrespective of genotype or vaccination status. Strong correlations were nonetheless present between RAWM performance and extent of "compact" Abeta deposition in both the hippocampus and the frontal cortex of vaccinated APP+PS1 mice. Our results suggest that the behavioral protection of long-term Abeta vaccinations is task specific, with preservation of hippocampal-associated working memory tasks most likely to occur. In view of the early short-term memory deficits exhibited by AD patients, Abeta vaccination of presymptomatic AD patients could be an effective therapeutic to protect against such cognitive impairments.