NEUROTROPHIC ACTION OF LIPOCORTIN-1 DERIVED FROM ASTROCYTES ON CULTURED RAT CORTICAL-NEURONS

The lipocortins are a family of structurally related proteins, namely an annexin family, that exerts a variety of cellular functions through Ca2+-dependent binding to phospholipase A(2) [EC 3.1.1.4], including a crucial role in the central nervous system (CNS) such as antipyrogen ic, thermoregulatory and neuroprotective agents in vivo. To elucidate the paradigm of lipocortin 1 functions in the CNS, we have first demon strated (1) the induction and subsequent extracellular secretion of LC 1 by glucocorticoid in cultured rat astrocytes, and (2) neurotrophic a ctivities (survival-promoting, neuritogenic and synaptogenic actions o n rat cortical neurons) of recombinant LC1. Time-and dose-dependent ex periments of a synthetic glucocorticoid, dexamethasone (DEX), on rat c ortical astrocytes in culture revealed that the expression of the intr acellular LC1 mRNA and protein were significantly augmented by DEX (1 mu M) In addition, DEX evoked an extracellular secretion of LC1 withou t its cytotoxic effects. Furthermore, the recombinant LC1 appeared to promote not only the survival and neurite outgrowth but also the synap togenesis of embryonal rat cortical neurons. These results suggest tha t LC1 induced and selectively released from astrocytes by either endog enously or exogenously introduced glucocorticoids may play a specific and essential role on development and regeneration of the central nerv ous system. (C) 1998 Elsevier Science B.V. All rights reserved.