Abstract

Dopamine neurons of the substantia nigra (SN) undergo a natural cell death event which is biphasic, with peaks at postnatal days (PNDs) 2 and 14. There is growing evidence that GDNF functions as a striatal target-derived neurotrophic factor to regulate the first phase. It has been unknown whether the GDNF receptor, GFRα1, may play a role in regulating either phase. To evaluate a possible role for GFRα1 we have examined its expression throughout postnatal development in the SN and particularly in the striatum, where its expression has been uncertain. GFRα1 mRNA is highly expressed in SN, as previously shown, with highest levels at PND14–28. We find that it is also expressed in striatum with a similar time course, but with a more discrete period of maximal expression between PND10 and PND14. The cellular basis of this maximum of expression is an increased number of GFRα1 mRNA-positive medium-sized neurons evenly distributed within the striatum. Immunostaining reveals GFRα1 protein-positive neurons with a similar morphology and distribution. We conclude that GFRα1 is expressed in striatum maximally late in postnatal development. In this location it may act in trans to influence the viability and development of nigral dopamine neurons.

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