Details

Autor(en) / Beteiligte

• Murphy, Diane D.
• Cole, Nelson B.
• Segal, Menahem

Titel

Brain-Derived Neurotrophic Factor Mediates Estradiol-Induced Dendritic Spine Formation in Hippocampal Neurons

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1998-09, Vol.95 (19), p.11412-11417

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition 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 selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons.