Growth/differentiation factor 5 protects nigrostriatal dopaminergic neurones in a rat model of Parkinson's disease.
Growth/differentiation factor 5 (GDF5), a novel member of the transforming growth factor beta superfamily, promotes the survival of dopaminergic neurones in vitro. We present here the first evidence for a neuroprotective action of GDF5 in vivo. We investigated the effects of intracerebral administration of GDF5 on a rat model of Parkinson's disease. GDF5 was administered just above the substantia nigra and into the lateral ventricle immediately before ipsilateral injection of 6-hydroxydopamine into the medial forebrain bundle. GDF5 prevented the development of amphetamine-induced rotations and preserved the integrity of striatal dopaminergic nerve terminals, as measured by positron emission tomography. Post-mortem studies showed that GDF5 spared dopamine levels in the striatum and tyrosine hydroxylase positive neurones in the midbrain. This study suggests that GDF5 has potential for the treatment of Parkinson's disease.
Sullivan
A M
AM
MRC Cyclotron Unit, Hammersmith Hospital, London, UK.
Opacka-Juffry
J
J
Hötten
G
G
Pohl
J
J
Blunt
S B
SB
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid