PMID- 17433270
OWN - NLM
STAT- MEDLINE
DCOM- 20070724
LR  - 20151119
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1150
DP  - 2007 May 30
TI  - beta-Estradiol induces synaptogenesis in the hippocampus by enhancing 
      brain-derived neurotrophic factor release from dentate gyrus granule cells.
PG  - 108-20
AB  - We investigated the effect of beta-estradiol (E2) on synaptogenesis in the 
      hippocampus using organotypic hippocampal slice cultures and subregional 
      hippocampal neuron cultures. E2 increased the expression of PSD95, a postsynaptic 
      marker, specifically in stratum lucidum of Cornu Ammonis 3 (CA3SL) in cultured 
      hippocampal slices. E2 also increased the spine density at the proximal site of 
      CA3 apical dendrites in CA3SL and PSD95 was clustered on these spine heads. The 
      effects of E2 on the expression of PSD95 and the spine density disappeared when 
      the dentate gyrus (DG) had been excised at 1 day in vitro (DIV). FM1-43 analysis 
      of subregional hippocampal neuron cultures which were comprised of Ammon's horn 
      neurons, DG neurons, or a mixture of these neurons, revealed that E2 increased 
      the number of presynaptic sites in the cultures that contained DG neurons. K252a, 
      a potent inhibitor of the high affinity receptor of brain-derived neurotrophic 
      factor (BDNF), and function-blocking antibody to BDNF (BDNFAB) completely 
      inhibited the effects of E2 in hippocampal slice cultures and subregional neuron 
      cultures, whereas ICI182,780 (ICI), a strong antagonist of nuclear estrogen 
      receptors (nERs), did not. Expression of BDNF in DG neurons was markedly higher 
      than that in Ammon's horn neurons and E2 did not affect these expression levels. 
      E2 significantly increased the BDNF release from DG neurons. KT5720, a specific 
      inhibitor of 3'-5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase 
      A (PKA), and Rp-adenosine 3', 5'-cyclic monophosphorothioate triethylammonium 
      salt (Rp-cAMP), a non-hydrolyzable diastereoisomer and a potent inhibitor of PKA, 
      completely suppressed the E2-induced increase in BDNF release, whereas ICI and 
      U0126, a potent inhibitor of MAP kinase kinase (MEK), did not. These results 
      suggest that E2 induces synaptogenesis between mossy fibers and CA3 neurons by 
      enhancing BDNF release from DG granule cells in a nER-independent and 
      PKA-dependent manner.
FAU - Sato, Kaoru
AU  - Sato K
AD  - Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, 
      Setagaya-ku, Tokyo 158-8501, Japan. kasato@nihs.go.jp
FAU - Akaishi, Tatsuhiro
AU  - Akaishi T
FAU - Matsuki, Norio
AU  - Matsuki N
FAU - Ohno, Yasuo
AU  - Ohno Y
FAU - Nakazawa, Ken
AU  - Nakazawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070313
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amino Acids)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (FM1 43)
RN  - 0 (Pyridinium Compounds)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (dolaisoleucine)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Amino Acids/metabolism
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Dendrites/drug effects/physiology
MH  - Dentate Gyrus/*cytology
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Estradiol/*pharmacology
MH  - Neurons/cytology/*drug effects
MH  - Organ Culture Techniques
MH  - Organogenesis/*drug effects
MH  - Pyridinium Compounds
MH  - Quaternary Ammonium Compounds
MH  - Rats
MH  - Rats, Wistar
MH  - Synapses/*physiology
EDAT- 2007/04/17 09:00
MHDA- 2007/07/25 09:00
CRDT- 2007/04/17 09:00
PHST- 2006/10/05 00:00 [received]
PHST- 2007/02/09 00:00 [revised]
PHST- 2007/02/28 00:00 [accepted]
PHST- 2007/04/17 09:00 [pubmed]
PHST- 2007/07/25 09:00 [medline]
PHST- 2007/04/17 09:00 [entrez]
AID - S0006-8993(07)00502-1 [pii]
AID - 10.1016/j.brainres.2007.02.093 [doi]
PST - ppublish
SO  - Brain Res. 2007 May 30;1150:108-20. doi: 10.1016/j.brainres.2007.02.093. Epub 
      2007 Mar 13.