PMID- 10900076
OWN - NLM
STAT- MEDLINE
DCOM- 20000829
LR  - 20131121
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 61
IP  - 3
DP  - 2000 Aug 1
TI  - Brain-derived neurotrophic factor and trkB are essential for cAMP-mediated 
      induction of the serotonergic neuronal phenotype.
PG  - 295-301
AB  - Serotonergic neurons in the central nervous system are crucial in the control of 
      autonomic functions and behavior. Mechanisms by which development and maintenance 
      of the serotonergic transmitter phenotype is regulated include activation of 
      protein kinase A (PKA). Using cultures established from the E14 rat raphe we show 
      here that forskolin (10 microM) increases numbers of neurons expressing 
      tryptophan hydroxylase (TpOH), the key enzyme of serotonin synthesis, and uptake 
      of the false serotonergic transmitter 5, 7-dihydroxytryptamine (5,7-DHT). As 
      shown by short-term treatments the effect is due to phenotype induction rather 
      than survival. To begin to understand downstream or parallel signaling pathways 
      required for the PKA-mediated induction of serotonergic markers, we have studied 
      the putative implication of brain-derived neurotrophic factor (BDNF) and its 
      receptor trkB. Treatment of raphe neurons with forskolin induced BDNF mRNA 
      assayed by competitive RT-PCR. Moreover, trkB-IgG receptor bodies fully prevented 
      the forskolin-induced numerical increase in TpOH- and 5,7-DHT-positive cells 
      suggesting an implication of a TrkB-activated pathway. TrkC-IgG had no effect. 
      K252b, a specific inhibitor of trk kinase activity likewise abolished the 
      induction of serotonergic markers by forskolin. In turn, the inductive effect of 
      BDNF on serotonergic markers was blocked by KT5720, a specific inhibitor of PKA. 
      Taken together, these data suggest that co-activation of cAMP- and trkB-dependent 
      signaling pathways plays a crucial role in the regulation of the serotonergic 
      neuronal phenotype.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Galter, D
AU  - Galter D
AD  - Neuroanatomy and Center for Neuroscience, University of Heidelberg, Im 
      Neuenheimer Feld 307, Heidelberg, Germany.
FAU - Unsicker, K
AU  - Unsicker K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Receptors, Serotonin, 5-HT1)
RN  - 1F7A44V6OU (Colforsin)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - 5,7-Dihydroxytryptamine/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Carbazoles/pharmacology
MH  - Cells, Cultured
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/*physiology
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Indole Alkaloids
MH  - Neurons/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Raphe Nuclei/cytology
MH  - Rats
MH  - Receptor, trkB/antagonists & inhibitors/*physiology
MH  - Receptors, Serotonin/physiology
MH  - Receptors, Serotonin, 5-HT1
MH  - Serotonin/*metabolism
MH  - Tryptophan Hydroxylase/metabolism
EDAT- 2000/07/19 11:00
MHDA- 2000/09/02 11:01
CRDT- 2000/07/19 11:00
PHST- 2000/07/19 11:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/07/19 11:00 [entrez]
AID - 10.1002/1097-4547(20000801)61:3<295::AID-JNR7>3.0.CO;2-4 [pii]
AID - 10.1002/1097-4547(20000801)61:3<295::AID-JNR7>3.0.CO;2-4 [doi]
PST - ppublish
SO  - J Neurosci Res. 2000 Aug 1;61(3):295-301. doi: 
      10.1002/1097-4547(20000801)61:3<295::AID-JNR7>3.0.CO;2-4.