Role of heparin binding growth factors in nigrostriatal dopamine system development and Parkinson's disease.
The developmental biology of the dopamine (DA) system may hold important clues to its reconstruction. We hypothesized that factors highly expressed during nigrostriatal development and re-expressed after injury and disease may play a role in protection and reconstruction of the nigrostriatal system. Examination of gene expression in the developing striatum suggested an important role for the heparin binding growth factor family at time points relevant to establishment of dopaminergic innervation. Midkine, pleiotrophin (PTN), and their receptors syndecan-3 and receptor protein tyrosine phosphatase beta/zeta, were highly expressed in the striatum during development. Furthermore, PTN was up-regulated in the degenerating substantia nigra of Parkinson's patients. The addition of PTN to ventral mesencephalic cultures augmented DA neuron survival and neurite outgrowth. Thus, PTN was identified as a factor that plays a role in the nigrostriatal system during development and in response to disease, and may therefore be useful for neuroprotection or reconstruction of the DA system.
Marchionini
Deanna M
DM
Dept. Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. deanna_marchionini@rush.edu
Lehrmann
Elin
E
Chu
Yaping
Y
He
Bin
B
Sortwell
Caryl E
CE
Becker
Kevin G
KG
Freed
William J
WJ
Kordower
Jeffrey H
JH
Collier
Timothy J
TJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D000078792:Midkine; D017072:Neostriatum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012016:Reference Values; D013378:Substantia Nigra / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism; D053670:Syndecan-3 / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D053670:Syndecan-3; C066845:pleiotrophin; D000078792:Midkine; D020794:Receptor Protein-Tyrosine Kinases; D004298:Dopamine