PMID- 19355925
OWN - NLM
STAT- MEDLINE
DCOM- 20090625
LR  - 20220408
IS  - 1875-5739 (Electronic)
IS  - 1567-2026 (Linking)
VI  - 6
IP  - 1
DP  - 2009 Feb
TI  - Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem 
      cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling 
      pathways.
PG  - 42-53
AB  - Neurospheres can be generated from the mouse fetal forebrain by exposing 
      multipotent neural stem cells (NSCs) to epidermal growth factor (EGF). In the 
      presence of EGF, NSCs can proliferate continuously while retaining the potential 
      to differentiate into neurons, astrocytes and oligodendrocytes. We examined the 
      expression pattern of the neurotrophin (NT) receptors tropomysin-related kinase 
      (TRK)-A, TRK-B, TRK-C and p75 neurotrophin receptor (p75(NTR)) in NSCs and the 
      corresponding lineage cells. Furthermore, we analyzed the action of the NT 
      Brain-Derived Neurotrophic Factor (BDNF) on NSCs' behavior. The effects of BDNF 
      on NSC proliferation and differentiation were examined together with the 
      signaling pathways by which BDNF receptors transduce signaling effects. We found 
      that all the known NT receptors, including the truncated isoforms of TRK-B 
      (t-TRK-B) and TRK-C (t-TRK-C), were expressed by Nestin-positive cells within the 
      neurosphere. Proliferation was enhanced in Nestin-positive and BrdU-positive 
      cells in the presence of BDNF. In particular, we show that t-TRK-B was abundantly 
      expressed in NSCs and the corresponding differentiated glia cells while full 
      length TRK-B (fl-TRK-B) was expressed in fully differentiated post-mitotic 
      neurons such as the neuronal cells of the newborn mouse cortex, suggesting that 
      BDNF may exert its proliferative effects on NSCs through the t-TRK-B receptor. 
      Finally, we analyzed the cell fates of NSCs differentiated with BDNF in the 
      absence of EGF and we demonstrate that BDNF stimulated the formation of 
      differentiated cell types in different proportions through the MAP kinase, AKT 
      and STAT-3 signaling pathways. Thus, the in-vivo regulation of neurogenesis may 
      be mediated by the summation of signals from the BDNF receptors, in particular 
      the t-TRK-B receptor, regulating physiological fates as diverse as normal neural 
      replacement, excessive neural loss, or tumor development.
FAU - Islam, Omedul
AU  - Islam O
AD  - Department of Molecular and Cell Biology, School of Biological Sciences, College 
      of Science, Nanyang Technological University, Singapore.
FAU - Loo, Tze X
AU  - Loo TX
FAU - Heese, Klaus
AU  - Heese K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Neurovasc Res
JT  - Current neurovascular research
JID - 101208439
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cerebral Cortex/cytology
MH  - Embryo, Mammalian
MH  - Embryonic Stem Cells/*drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/pharmacology
MH  - Female
MH  - Green Fluorescent Proteins/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Neuroblastoma
MH  - Neurons/*physiology
MH  - Oncogene Protein v-akt/metabolism
MH  - Pregnancy
MH  - Rats
MH  - Receptor, trkB/*metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Transfection/methods
EDAT- 2009/04/10 09:00
MHDA- 2009/06/26 09:00
CRDT- 2009/04/10 09:00
PHST- 2009/04/10 09:00 [entrez]
PHST- 2009/04/10 09:00 [pubmed]
PHST- 2009/06/26 09:00 [medline]
AID - 10.2174/156720209787466028 [doi]
PST - ppublish
SO  - Curr Neurovasc Res. 2009 Feb;6(1):42-53. doi: 10.2174/156720209787466028.