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Postnatal developmental programmed cell death in dopamine neurons.

Robert E Burke1

  • 1Department of Neurology, The College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. rb43@columbia.edu

Annals of the New York Academy of Sciences
|July 9, 2003
PubMed
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Dopamine neuron development involves natural cell death regulated by target interaction. Glial cell-derived neurotrophic factor (GDNF) uniquely supports dopamine neuron survival by suppressing apoptosis during this critical period.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Dopamine (DA) neurons in the substantia nigra (SN) undergo prenatal development (birth, specification, migration) and postnatal development (axon extension, differentiation, synapse formation).
  • A natural, biphasic apoptotic cell death event occurs postnatally, peaking on postnatal days 2 and 14, largely subsiding by day 20.
  • This cell death is regulated by interaction with the striatal target, with evidence of target dependence within the first two postnatal weeks.

Purpose of the Study:

  • To investigate the role of striatal target-derived neurotrophic factors in regulating the natural apoptotic cell death of developing dopamine neurons.
  • To identify specific factors that support the viability of mesencephalic dopamine neurons during postnatal development.

Main Methods:

Related Experiment Videos

  • Utilized a postnatal primary culture model of mesencephalic dopamine neurons.
  • Administered glial cell-derived neurotrophic factor (GDNF) in vivo via intrastriatal injection.
  • Used neutralizing antibodies against GDNF in vivo.

Main Results:

  • Glial cell-derived neurotrophic factor (GDNF) was found to be uniquely capable of supporting dopamine neuron viability by suppressing apoptosis in vitro.
  • Intrastriatal injection of GDNF in vivo suppressed dopamine neuron apoptosis.
  • Administration of neutralizing antibodies against GDNF augmented dopamine neuron apoptosis.

Conclusions:

  • Glial cell-derived neurotrophic factor (GDNF) plays a crucial role in regulating the natural apoptotic cell death of developing dopamine neurons.
  • GDNF is a strong candidate for a striatum-derived neurotrophic factor essential for dopamine neuron survival during development.