PMID- 9634558
OWN - NLM
STAT- MEDLINE
DCOM- 19980702
LR  - 20220309
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 18
IP  - 13
DP  - 1998 Jul 1
TI  - Neurturin exerts potent actions on survival and function of midbrain dopaminergic 
      neurons.
PG  - 4929-37
AB  - Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on 
      survival and function of midbrain dopaminergic (DA) neurons in a variety of 
      models. Although other growth factors expressed in the vicinity of developing DA 
      neurons have been reported to support survival of DA neurons in vitro, to date 
      none of these factors duplicate the potent and selective actions of GDNF in vivo. 
      We report here that neurturin (NTN), a homolog of GDNF, is expressed in the 
      nigrostriatal system, and that NTN exerts potent effects on survival and function 
      of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially 
      expressed in the ventral midbrain and striatum during development and that NTN 
      exhibits survival-promoting actions on both developing and mature DA neurons. In 
      vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct 
      injection of NTN into the substantia nigra protects mature DA neurons from cell 
      death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of 
      intact adult animals induces behavioral and biochemical changes associated with 
      functional upregulation of nigral DA neurons. The similarity in potency and 
      efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to 
      the differential distribution of the receptor components GDNF Family Receptor 
      alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results 
      suggest that NTN is an endogenous trophic factor for midbrain DA neurons and 
      point to the possibility that GDNF and NTN may exert redundant trophic influences 
      on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
FAU - Horger, B A
AU  - Horger BA
AD  - Department of Neuroscience, Genentech, South San Francisco, California 94080, 
      USA.
FAU - Nishimura, M C
AU  - Nishimura MC
FAU - Armanini, M P
AU  - Armanini MP
FAU - Wang, L C
AU  - Wang LC
FAU - Poulsen, K T
AU  - Poulsen KT
FAU - Rosenblad, C
AU  - Rosenblad C
FAU - Kirik, D
AU  - Kirik D
FAU - Moffat, B
AU  - Moffat B
FAU - Simmons, L
AU  - Simmons L
FAU - Johnson, E Jr
AU  - Johnson E Jr
FAU - Milbrandt, J
AU  - Milbrandt J
FAU - Rosenthal, A
AU  - Rosenthal A
FAU - Bjorklund, A
AU  - Bjorklund A
FAU - Vandlen, R A
AU  - Vandlen RA
FAU - Hynes, M A
AU  - Hynes MA
FAU - Phillips, H S
AU  - Phillips HS
LA  - eng
GR  - R01 AG013729/AG/NIA NIH HHS/United States
GR  - R01 AG013730/AG/NIA NIH HHS/United States
GR  - R01AG13729/AG/NIA NIH HHS/United States
GR  - R01AG13730/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Gdnf protein, mouse)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurturin)
RN  - 0 (Nrtn protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sympatholytics)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/analysis
MH  - Animals
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Corpus Striatum/*cytology/embryology
MH  - Disease Models, Animal
MH  - Dopamine/analysis/*physiology
MH  - Gene Expression Regulation, Developmental/physiology
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Mice
MH  - Nerve Growth Factors/*genetics/pharmacology
MH  - Nerve Tissue Proteins/pharmacology
MH  - Neurons/chemistry/*cytology/drug effects
MH  - Neuroprotective Agents/pharmacology
MH  - Neurturin
MH  - Nucleus Accumbens/cytology/embryology
MH  - Oxidopamine
MH  - Parkinson Disease, Secondary/drug therapy/pathology
MH  - RNA, Messenger/analysis
MH  - Substantia Nigra/*cytology/embryology
MH  - Sympatholytics
PMC - PMC6792569
EDAT- 1998/06/23 02:01
MHDA- 2001/03/28 10:01
PMCR- 1999/01/01
CRDT- 1998/06/23 02:01
PHST- 1998/06/23 02:01 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/06/23 02:01 [entrez]
PHST- 1999/01/01 00:00 [pmc-release]
AID - 2109 [pii]
AID - 10.1523/JNEUROSCI.18-13-04929.1998 [doi]
PST - ppublish
SO  - J Neurosci. 1998 Jul 1;18(13):4929-37. doi: 10.1523/JNEUROSCI.18-13-04929.1998.