PMID- 17298183
OWN - NLM
STAT- MEDLINE
DCOM- 20071011
LR  - 20181113
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 5
IP  - 3
DP  - 2007 Mar
TI  - Absence of Ret signaling in mice causes progressive and late degeneration of the 
      nigrostriatal system.
PG  - e39
LID - e39
AB  - Support of ageing neurons by endogenous neurotrophic factors such as glial cell 
      line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor 
      (BDNF) may determine whether the neurons resist or succumb to neurodegeneration. 
      GDNF has been tested in clinical trials for the treatment of Parkinson disease 
      (PD), a common neurodegenerative disorder characterized by the loss of midbrain 
      dopaminergic (DA) neurons. BDNF modulates nigrostriatal functions and rescues DA 
      neurons in PD animal models. The physiological roles of GDNF and BDNF signaling 
      in the adult nigrostriatal DA system are unknown. We generated mice with 
      regionally selective ablations of the genes encoding the receptors for GDNF (Ret) 
      and BDNF (TrkB). We find that Ret, but not TrkB, ablation causes progressive and 
      adult-onset loss of DA neurons specifically in the substantia nigra pars 
      compacta, degeneration of DA nerve terminals in striatum, and pronounced glial 
      activation. These findings establish Ret as a critical regulator of long-term 
      maintenance of the nigrostriatal DA system and suggest conditional Ret mutants as 
      useful tools for gaining insights into the molecular mechanisms involved in the 
      development of PD.
FAU - Kramer, Edgar R
AU  - Kramer ER
AD  - Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology, 
      Martinsried, Germany. ekramer@neuro.mpg.de
FAU - Aron, Liviu
AU  - Aron L
FAU - Ramakers, Geert M J
AU  - Ramakers GM
FAU - Seitz, Sabine
AU  - Seitz S
FAU - Zhuang, Xiaoxi
AU  - Zhuang X
FAU - Beyer, Klaus
AU  - Beyer K
FAU - Smidt, Marten P
AU  - Smidt MP
FAU - Klein, Rudiger
AU  - Klein R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (Ret protein, mouse)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Corpus Striatum/metabolism/*pathology
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Proto-Oncogene Proteins c-ret/*metabolism
MH  - Receptor, trkB/genetics
MH  - *Signal Transduction
MH  - Substantia Nigra/metabolism/*pathology
PMC - PMC1808500
COIS- Competing interests. The authors have declared that no competing interests exist.
EDAT- 2007/02/15 09:00
MHDA- 2007/10/12 09:00
PMCR- 2007/02/13
CRDT- 2007/02/15 09:00
PHST- 2006/06/12 00:00 [received]
PHST- 2006/12/07 00:00 [accepted]
PHST- 2007/02/15 09:00 [pubmed]
PHST- 2007/10/12 09:00 [medline]
PHST- 2007/02/15 09:00 [entrez]
PHST- 2007/02/13 00:00 [pmc-release]
AID - 1544-9173-5-3-e39 [pii]
AID - 06-PLBI-RA-1019R1 [pii]
AID - 10.1371/journal.pbio.0050039 [doi]
PST - ppublish
SO  - PLoS Biol. 2007 Mar;5(3):e39. doi: 10.1371/journal.pbio.0050039.