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SummaryAging is a complex, multifactorial process. One of the features of normal aging of the brain is a decline in cognitive functions and much experimental attention has been devoted to understanding this process. Evidence accumulated in the last decade indicates that such functional changes are not due to gross morphological alterations, but to subtle functional modification of synaptic connectivity and intracellular signalling and metabolism. Such synaptic modifications are compatible with a normal level of activity and allow the maintenance of a certain degree of functional reserve. This is in contrast to the changes in various neurodegenerative diseases, characterized by significant neuronal loss and dramatic and irreversible functional deficit. This whole special issue has been initiated with the intention of focusing on the processes of normal brain aging. In this review, we present data that shows how subtle changes in Ca 2+ homeostasis or in the state of various Ca 2+ -dependent processes or molecules, which occur in aging can have significant functional consequences.

International audienceSphingosine 1-phosphate (S1P) receptor expression and the effects of S1P on migration were studied in one papillary (NPA), two follicular (ML-1, WRO) and two anaplastic (FRO, ARO) thyroid cancer cell lines, as well as in human thyroid cells in primary culture. Additionally, the effects of S1P on proliferation, adhesion and calcium signalling were addressed in ML-1 and FRO cells. All cell types expressed multiple S1P receptors. S1P evoked intracellular calcium signalling in primary cultures, ML-1 cells and FRO cells. Neither proliferation nor migration was affected in primary cultures, whereas S1P partly inhibited proliferation in ML-1 and FRO cells. Low nanomolar concentrations of S1P inhibited migration in FRO, WRO and ARO cells, but stimulated ML-1 cell migration. Consistently, S1P 1} and S1P 3}, which mediate migratory responses, were strongly expressed in ML-1 cells and S1P 2}, which inhibits migration, was the dominating receptor in the other cell lines. The migratory effect in ML-1 cells was mediated by G i} and phosphatidylinositol 3-kinase. Both S1P and the S1P 1}-specific agonist SEW-2871 induced Akt phosphorylation at Ser-473. However, SEW-2871 failed to stimulate migration, whereas the S1P 1}/S1P 3} antagonist VPC 23019 inhibited S1P-induced migration. The results implicate that aberrant S1P receptor expression may enhance thyroid cancer cell migration and thus contribute to the metastatic behaviour of some thyroid tumours

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