Neurotrophic action of lipocortin 1 derived from astrocytes on cultured rat cortical neurons

Abstract The lipocortins are a family of structurally related proteins, namely an annexin family, that exerts a variety of cellular functions through Ca 2+ -dependent binding to phospholipase A 2 [EC 3.1.1.4], including a crucial role in the central nervous system (CNS) such as antipyrogenic, thermoregulatory and neuroprotective agents in vivo. To elucidate the paradigm of lipocortin 1 functions in the CNS, we have first demonstrated (1) the induction and subsequent extracellular secretion of LC1 by glucocorticoid in cultured rat astrocytes, and (2) neurotrophic activities (survival-promoting, neuritogenic and synaptogenic actions on rat cortical neurons) of recombinant LC1. Time-and dose-dependent experiments of a synthetic glucocorticoid, dexamethasone (DEX), on rat cortical astrocytes in culture revealed that the expression of the intracellular LC1 mRNA and protein were significantly augmented by DEX (1 μM). In addition, DEX evoked an extracellular secretion of LC1 without its cytotoxic effects. Furthermore, the recombinant LC1 appeared to promote not only the survival and neurite outgrowth but also the synaptogenesis of embryonal rat cortical neurons. These results suggest that LC1 induced and selectively released from astrocytes by either endogenously or exogenously introduced glucocorticoids may play a specific and essential role on development and regeneration of the central nervous system.