GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF), a recently cloned
new member of the transforming growth factor-beta superfamily, promote
s survival of cultured fetal mesencephalic dopamine neurons(1) and is
expressed in the developing striatum(2,3). There have, however, been n
o reports about effects of GDNF in situ. We have used the dopaminergic
neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which
produces parkinsonian symptoms in man, to determine whether GDNF migh
t exert protective or regenerative effects in vivo in the adult nigros
triatal dopamine system in C57/Bl mice. GDNF injected over the substan
tia nigra or in striatum before MPTP potently protects the dopamine sy
stem, as shown by numbers of mesencephalic dopamine nerve cell bodies,
dopamine nerve terminal densities and dopamine levels. When GDNF is g
iven after MPTP, dopamine levels and fibre densities are significantly
restored. In both cases, motor behaviour is increased above,normal le
vels. We conclude that intracerebral GDNF administration exerts both p
rotective and reparative effects on the nigrostriatal dopamine system,
which may have implications for the development of new treatment stra
tegies for Parkinson's disease.