Calcium dysregulation in neuronal aging and Alzheimer's disease: history and new directions.
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Biomedical subjects
Publications and source records attributed to K C Chen.
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There is growing evidence that alterations in calcium (Ca2+) homeostasis may play a role in processes of brain aging and neurodegeneration. There also is evidence that some of the altered Ca2+ homeostasis in hippocampal neurons may arise from an increased density of L-type voltage sensitive Ca2+ channels (L-VSCC). In the present studies, we tested the possibility that previously observed increases in functional L-VSCC with aging might be related to up-regulated gene/mRNA expression for Ca2+ channel subunits. A significant aging-related increase in mRNA content for the alpha1D subunit of the L-type VSCC was observed in hippocampus of aged F344 rats (25 months old) relative to young (4 months old) and middle-aged animals (13 months old), as assessed by both in situ hybridization analyses (densitometry and grain density) and ribonuclease protection assay (RPA). In RPA analyses, the alpha1C subunit mRNA also showed a significant increase in 25-month-old rats. No age changes were seen in mRNA for the beta1b subunit of VSCC or for GAPDH, a standard control. The clearest increases in alpha1D mRNA expression were observed in subfield CA1, with little or no change seen in dentate gyrus. Although these results alone do not demonstrate that mRNA/gene expression changes contribute directly to changes in functional Ca2+ channels, they clearly fulfill an important prediction of that hypothesis. Therefore, these studies may have important implications for the role of gene expression in aging-dependent alterations in brain Ca2+ homeostasis.
The prevalence of nonspecific vaginitis was 24% among 98 randomly selected women examined at a clinic for sexually transmitted diseases and 32% among 135 women with suspected cervicitis at the same clinic. Mycoplasma hominis was isolated more often and serum antibody levels to M. hominis were higher in women with nonspecific vaginitis than in women without nonspecific vaginitis. Similarly, the rate of isolation of Gardnerella vaginalis and the quantitative growth of G. vaginalis were higher for women with nonspecific vaginitis. Abnormal results of gasliquid chromatographic analysis of vaginal fluid and the presence of abnormal diamines in the vaginal fluid also were associated with nonspecific vaginitis and with the isolation of M. hominis, whether or not G. vaginalis was isolated. Further studies of the ecologic interactions among M. hominis, G. vaginalis, and anaerobes in nonspecific vaginitis are needed for a better understanding of the pathogenesis of this syndrome.