Regulation of brain-derived neurotrophic factor messenger RNA levels in avian hypothalamic slice cultures

Mechanisms regulating the expression of brain-derived neurotrophic factor, a member of the neurotrophin family, have been extensively studied in the r at cerebral cortex, hippocampus and cerebellum. In contrast, little is know n regarding the regulation of this growth factor in the hypothalamus. Here we present an analysis of the regulation of brain-derived neurotrophic fact or messenger RNA levels in chick embryo hypothalamic slice cultures followi ng exposure to potassium chloride, glutamate agonists and sex steroids. Fol lowing a week in chemically-defined media the tissue was depolarized by exp osure to 50 mM potassium chloride for 6 h, resulting in a significant 4.2-f old increase in the level of brain-derived neurotrophic factor messenger RN A, This result is consistent with studies of other brain regions. Similar 6 -h acute exposures of the hypothalamic cultures to 25 mu M N-methyl-D-aspar tic acid, 25 mu M kainic acid and 25 mu M alpha-amino-3-hydroxy-5-methyl-is oxazole-4-propionic acid also significantly increased messenger RNA levels 2.5-, 2.1- and 1.4-fold, respectively. It was previously reported that brai n-derived neurotrophic factor levels within the rat cerebral cortex, olfact ory bulb and hippocampus are altered by exposure to 17 beta-estradiol. Here we show that in hypothalamic slice cultures neither acute nor chronic trea tments with 10 and 100 nM 17 beta-estradiol and 10 nM testosterone signific antly altered the steady-state level of this growth factor. These findings show that neuronal activity, induced by glutamate agonists a nd potassium chloride, can regulate brain-derived neurotrophic factor messe nger RNA levels within embryonic hypothalamic slice cultures. This regulati on could play a critical role in the modulation of programmed cell death an d synaptic maturation during development of the hypothalamus. (C) 2000 IBRO . Published by Elsevier Science Ltd. All rights reserved.