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Spatial and temporal growth factor influences on developing midbrain dopaminergic neurons

J Engele1

  • 1Anatomie und Zellbiologie, Universität Ulm, Germany.

Journal of Neuroscience Research
|August 26, 1998
PubMed
Summary

Early embryonic dopaminergic neuron survival is promoted by glial-derived growth factors, while later stages rely on autocrine factors. This study investigates growth factor roles in developing dopaminergic neurons.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Dopaminergic neurons are crucial for motor control and cognition.
  • In vitro studies identify numerous growth factors affecting dopaminergic neuron survival and differentiation.
  • The in vivo roles of these growth factors during dopaminergic neuron development remain largely unknown.

Purpose of the Study:

  • To investigate the influence of glial and neuronal factors on dopaminergic cell survival during embryonic development in vivo.
  • To determine the developmental stage-specific roles of growth factors in dopaminergic neuron survival.

Main Methods:

  • Serum-free dissociated cell cultures of embryonic day (E) 15 and E17 rat mesencephalon were used.
  • Cultures were exposed to media conditioned by glia and neurons from mesencephalic, striatal, and cortical regions.

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  • Dopaminergic neuron survival was assessed by counting tyrosine hydroxylase-immunoreactive cells.
  • The effects of specific growth factors (BDNF, GDNF) and a MAP kinase inhibitor (PD98059) were evaluated.
  • Main Results:

    • Glial-conditioned media from mesencephalon, striatum, and cortex significantly increased dopaminergic neuron survival in E15 cultures (up to 2.6-fold).
    • Glial-conditioned media had no effect on dopaminergic neuron survival in E17 cultures.
    • Neuronal-conditioned media from striatal and mesencephalic neurons did not affect E17 dopaminergic neuron survival.
    • E17 dopaminergic neurons remained sensitive to growth factors, as evidenced by PD98059-induced decline in survival and promotion by BDNF and GDNF (1.5- to 1.9-fold).

    Conclusions:

    • Dopaminergic cell survival during early embryonic development is primarily influenced by unknown glial-derived growth factors from the mesencephalon, cortex, and striatum.
    • During later developmental stages, survival is predominantly mediated by autocrine-acting growth factors like BDNF and GDNF.
    • These findings highlight a shift in the regulatory mechanisms of dopaminergic neuron survival throughout embryonic development.