GDNF MESSENGER-RNA EXPRESSION IN NORMAL POSTNATAL-DEVELOPMENT, AGING, AND IN WEAVER MUTANT MICE

Glial cell line-derived neurotrophic factor (GDNF) has been demonstrated to enhance the survival and process outgrowth of mesencephalic dopamine neurons. A nuclease protection assay was utilized to determine whether GDNF mRNA is expressed in the ventral mesencephalon and/or striatum during normal mouse postnatal development. While no GDNF mRNA was detected in the ventral mesencephalon, expression was detected in the striatum throughout postnatal development and maturity with the peak of expression being in the second postnatal week. In the process of nor mal aging, no change in the levels of GDNF mRNA was observed in the striatum, while a 10-fold increase in glial fibrillary acid protein (GFAP) mRNA was detected in 24-month-old relative to either 4.5- or Ii-month-old mice. Further analysis addressed whether there are changes in GDNF gene expression associated with the neurodegeneration of dopamine neurons that occurs in the weaver mutant mouse. A transient 65% increase in the expression of GDNF mRNA was observed in weaver mutant striatum on postnatal day 22. The results of this study suggest that GDNF could provide target derived dopaminergic neurotrophic support and stimulate fiber outgrowth during development and that decreased levels of GDNF expression are not responsible for either aging-associated decreases in dopaminergic neuronal plasticity or neurodegeneration in the weaver mutant mouse.