MAGNOCELLULAR VASOPRESSINERGIC NEURONS IN EXPLANT CULTURES ARE RESCUED FROM CELL-DEATH BY CILIARY NEUROTROPHIC FACTOR AND LEUKEMIA INHIBITING FACTOR

Selective death of magnocellular vasopressinergic neurons in the hypot halamus has been reported in cases of hereditary and idiopathic diabet es insipidus and after experimental lesions of the hypothalamo-neurohy pophyseal pathway, To identify trophic factors that promote survival o f these neurons, an in vitro model system was established in which org anotypic cultures of the rat hypothalamic paraventricular nucleus were maintained in chemically-defined medium. We observe that the majority of magnocellular vasopressinergic neurons dir in these cultures, whil e other cell populations such as corticotrophin-releasing factor produ cing parvicellular and oxytocin producing magnocellular cells retain a well preserved cytoarchitectonic organization. Degenerating vasopress inergic cells exhibit morphological signs of apoptosis and stained pos itively when analysed by the terminal deoxynucleotidyl transferase bio tinylated dUTP nick end-labelling assay. Partial survival of vasopress inergic neurons occurred after co-culturing the paraventricular nucleu s with neurohypophyseal explants, indicating that target-derived facto rs may be required for the survival of these neurons. Cell survival is dramatically increased by the administration of ciliary neurotrophic factor and leukemia inhibiting factor, bur not by interleukin 6 or the members of the neurotrophin family. Reverse transcription-polymerase chain reaction followed by Southern analysis shows the presence of cil iary neurotrophic factor messenger RNA in the neurohypophysis. Thus, e ndogenous ciliary neurotrophic factor and leukemia inhibiting factor, produced by neurohypophyseal cells may function as a physiological sur vival factor for neurosecretory vasopressinergic neurons. (C) 1998 IBR O. Published by Elsevier Science Ltd.