Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons
AUTOR(ES)
Murphy, Diane D.
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21656Documentos Relacionados
- Nitric oxide down-regulates brain-derived neurotrophic factor secretion in cultured hippocampal neurons
- Essential role of brain-derived neurotrophic factor in adult hippocampal function
- Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.
- Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
- Timing of brain-derived neurotrophic factor exposure affects life expectancy of new neurons