PMID- 11592117
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20191210
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 66
IP  - 2
DP  - 2001 Oct 15
TI  - Estrogen stimulates brain-derived neurotrophic factor expression in embryonic 
      mouse midbrain neurons through a membrane-mediated and calcium-dependent 
      mechanism.
PG  - 221-30
AB  - We have provided evidence that 17beta-estradiol (E) synthesized in the midbrain 
      promotes the differentiation of midbrain dopamine neurons through nonclassical 
      steroid action. Because these developmental effects resemble those reported for 
      brain-derived neurotrophic factor (BDNF), we hypothesized that E influences 
      dopaminergic cell differentiation through a BDNF-dependent mechanism. Competitive 
      RT-PCR and ELISA techniques were employed to study first the developmental 
      pattern of BDNF and trkB expression in the mouse midbrain. BDNF protein/mRNA 
      levels peaked postnatally, whereas trkB did not fluctuate perinatally. To prove 
      the hypothesis that E regulates BDNF expression in vivo, fetuses and newborns 
      were treated with the aromatase antagonist CGS 16949A. CGS 16949A exposure 
      reduced midbrain BDNF mRNA/protein levels. The coapplication of CGS 16949A and E 
      abolished this effect. Midbrain cultures from mouse fetuses were used to 
      investigate intracellular signaling mechanisms involved in transmitting E 
      effects. Estrogen increased expression of BDNF but not of other neurotrophins. As 
      concerns the related signaling mechanism, these effects were antagonized by 
      interrupting intracellular Ca(2+) signaling with BAPTA and thapsigargin but not 
      by the estrogen receptor antagonist ICI 182,780. Insofar as E effects on BDNF 
      mRNA expression were inhibited by cycloheximide, it appears likely that other, 
      not yet characterized intermediate proteins take part in the estrogenic 
      regulation of BDNF expression. We conclude that E exerts its stimulatory effect 
      on the differentiation of dopaminergic neurons by coordinating BDNF expression. 
      This particular E effect appears to be transmitted through Ca(2+)-dependent 
      signaling cascades upon activation of putative membrane estrogen receptors.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Ivanova, T
AU  - Ivanova T
AD  - Abteilung Anatomie und Zellbiologie, Universitat Ulm, 89069 Ulm, Germany.
FAU - Kuppers, E
AU  - Kuppers E
FAU - Engele, J
AU  - Engele J
FAU - Beyer, C
AU  - Beyer C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoquinolines)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - H3988M64PU (Fadrozole)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Aromatase Inhibitors
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cells, Cultured/drug effects/metabolism
MH  - Culture Media, Serum-Free
MH  - Cycloheximide/pharmacology
MH  - Egtazic Acid/*analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estradiol/*analogs & derivatives/*pharmacology
MH  - Fadrozole/pharmacology
MH  - Female
MH  - Fulvestrant
MH  - Gene Expression Regulation/*drug effects
MH  - Isoquinolines/pharmacology
MH  - Male
MH  - Mesencephalon/*cytology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nerve Growth Factors/pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkB/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - *Sulfonamides
MH  - Thapsigargin/pharmacology
EDAT- 2001/10/10 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/10 10:00
PHST- 2001/10/10 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/10 10:00 [entrez]
AID - 10.1002/jnr.1214 [pii]
AID - 10.1002/jnr.1214 [doi]
PST - ppublish
SO  - J Neurosci Res. 2001 Oct 15;66(2):221-30. doi: 10.1002/jnr.1214.