BRAIN-DERIVED NEUROTROPHIC FACTOR MEDIATES ESTRADIOL-INDUCED DENDRITIC SPINE FORMATION IN HIPPOCAMPAL-NEURONS

Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to indu ce an increase of dendritic spine density on hippocampal neurons in vi vo and in vitro. The neurotrophin brain-derived neurotrophic factor (B DNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons, We now demonstrate that estr adiol do,vn-regulates BDNF in cultured hippocampal neurons to 40% of c ontrol values within 24 hr of exposure. This, in turn, decreases inhib ition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density, Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a se lective antisense oligonucleotide mimics the effects of estradiol. Add ition of BDNF antibodies also increases spine density, and diazepam, w hich facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link bet ween estradiol, BDNF as a potent regulator of GBBAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal ne urons.