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The Journal of Neuroscience, April 1, 2002, 22(7):2650-2659
Estrogen Regulates the Development of Brain-Derived Neurotrophic
Factor mRNA and Protein in the Rat Hippocampus
Derek T.
Solum1, 2 and
Robert J.
Handa1
1 Department of Anatomy and Neurobiology, Colorado
State University, Fort Collins, Colorado 80523, and
2 Department of Cell Biology, Neurobiology, and Anatomy,
Loyola University Chicago, Maywood, Illinois 60153
During development, estrogen has a variety of effects on
morphological and electrophysiological properties of hippocampal neurons. Brain-derived neurotrophic factor (BDNF) also plays an important role in the survival and differentiation of neurons during
development. We examined the effects of gonadectomy with and without
estrogen replacement on the mRNA and protein of BDNF and its receptor,
trkB, during early postnatal development of the rat hippocampus. We
used immunocytochemistry to demonstrate that estrogen receptor  (ER) and BDNF were localized to the same cells within the developing
hippocampus. BDNF and ER were colocalized in pyramidal cells of the
CA3 subregion and to a lesser extent in CA1. To determine whether BDNF
mRNA was regulated by estrogen during development, we gonadectomized
male rat pups at postnatal day 0 (P0) and examined mRNA and protein
levels from P0 to P25 using real-time reverse transcription-PCR and
Western blot analysis. After gonadectomy, BDNF mRNA levels are
significantly reduced on P7, but after treatment of
gonadectomized animals with estradiol benzoate on P0, levels at
all ages were similar to those in intact animals. BDNF mRNA changes
after gonadectomy are accompanied by an increase in the levels of BDNF
protein, which were reduced by estrogen treatment at P0. We also
examined the effect of postnatal estrogen treatment on trkB. There were
no significant changes in trkB mRNA or protein in gonadectomized or
estrogen-replaced animals. These results suggest that a direct
interaction may exist between ER and BDNF to alter hippocampal
physiology during development in the rat.
Key words:
estrogen; estrogen receptor; ER; BDNF; trkB; hippocampus; development
Copyright © 2002 Society for Neuroscience 0270-6474/02/2272650-10$05.00/0
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