GROWTH DIFFERENTIATION FACTOR-5 PROTECTS NIGROSTRIATAL DOPAMINERGIC-NEURONS IN A RAT MODEL OF PARKINSONS-DISEASE/

Growth/differentiation factor 5 (GDF5), a novel member of the transfor ming growth factor beta superfamily, promotes the survival of dopamine rgic neurones in vitro. We present here the first evidence for a neuro protective action of GDF5 in vivo. We investigated the effects of intr acerebral administration of GDF5 on a rat model of Parkinson's disease . GDF5 was administered just above the substantia nigra and into the l ateral ventricle immediately before ipsilateral injection of 6-hydroxy dopamine into the medial forebrain bundle. GDF5 prevented the developm ent of amphetamine-induced rotations and preserved the integrity of st riatal dopaminergic nerve terminals, as measured by positron emission tomography. Post-mortem studies showed that GDF5 spared dopamine level s in the striatum and tyrosine hydroxylase positive neurones in the mi dbrain. This study suggests that GDF5 has potential for the treatment of Parkinson's disease. (C) 1997 Elsevier Science Ireland Ltd.