PMID- 8283241
OWN - NLM
STAT- MEDLINE
DCOM- 19940216
LR  - 20220321
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 14
IP  - 1
DP  - 1994 Jan
TI  - Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on 
      cultured dopaminergic and GABAergic neurons of the ventral mesencephalon.
PG  - 335-47
AB  - The neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 
      (NT-3), and neurotrophin-4/5 (NT-4/5) were compared for their effects in 
      promoting the survival and/or regulation of expression of phenotypic markers of 
      dopaminergic and GABAergic neurons in cultures derived from embryonic rat ventral 
      mesencephalon. Dopaminergic neuron number and phenotypic expression were 
      monitored by tyrosine hydroxylase (TH) immunocytochemistry, and measurement of 
      high-affinity dopamine uptake activity and dopamine content, respectively. 
      High-affinity GABA uptake, glutamic acid decarboxylase (GAD) activity, and 
      endogenous GABA content were used to detect GABAergic neurons. Seven days of 
      treatment with either BDNF or NT-3 resulted in dose-dependent increases in the 
      number of TH-positive neurons, with maximal responses of 3-fold and 2.3-fold, 
      respectively. Dopamine uptake activity and dopamine content were similarly 
      increased. The effects of BDNF and NT-3 on dopamine uptake activity showed no 
      additivity. NT-4/5 treatment elicited the greatest increase (7-fold) in the 
      number of TH-positive neurons, as well as a 2.6-fold increase in dopamine 
      content. In marked contrast to BDNF or NT-3, NT-4/5 had no effect on dopamine 
      uptake capacity. BDNF, NT-3, or NT-4/5 also produced dose-dependent elevations of 
      2-3-fold in GABA uptake activity. These effects were not additive. GAD activity 
      was increased by BDNF (1.8-fold) and NT-3 (threefold) treatment, but not by 
      NT-4/5, whereas GABA content was increased to a similar extent by all three 
      neurotrophins. NGF had no effect on any of the parameters measured in this study. 
      Northern analyses indicated that the mRNAs encoding TrkB and TrkC, the functional 
      high-affinity receptors for BDNF and NT-4/5, and NT-3, respectively, are 
      expressed in the substantia nigra of adult rat brain, as well as in cultures of 
      developing ventral mesencephalon. Taken together, our results indicate that BDNF 
      and NT-3 have broadly similar effects in promoting the survival and 
      differentiated phenotype of both dopaminergic and GABAergic neurons of the 
      developing substantia nigra. Although BDNF and NT-4/5 are thought to act through 
      the same high-affinity receptor, TrkB, it is evident that these two neurotrophins 
      have distinct as well as overlapping actions toward mesencephalic dopaminergic or 
      GABAergic neurons.
FAU - Hyman, C
AU  - Hyman C
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
FAU - Juhasz, M
AU  - Juhasz M
FAU - Jackson, C
AU  - Jackson C
FAU - Wright, P
AU  - Wright P
FAU - Ip, N Y
AU  - Ip NY
FAU - Lindsay, R M
AU  - Lindsay RM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Receptors, Growth Factor)
RN  - 145172-44-7 (neurotrophin 5)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkC)
RN  - P658DCA9XD (neurotrophin 4)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor
MH  - Cells, Cultured
MH  - Dopamine/*metabolism
MH  - Mesencephalon/cytology/*drug effects/metabolism
MH  - Nerve Growth Factors/*pharmacology
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Neurotrophin 3
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptor, trkC
MH  - Receptors, Growth Factor/metabolism
MH  - Substantia Nigra/metabolism
MH  - Tissue Distribution
MH  - gamma-Aminobutyric Acid/*metabolism
PMC - PMC6576839
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
PMCR- 1994/07/01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
PHST- 1994/07/01 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.14-01-00335.1994 [doi]
PST - ppublish
SO  - J Neurosci. 1994 Jan;14(1):335-47. doi: 10.1523/JNEUROSCI.14-01-00335.1994.