The small molecule FKBP ligand GPI 1046 induces partial striatal re-innervation after intranigral 6-hydroxydopamine lesion in rats.
Extensive unilateral striatal deafferentation was produced by intranigral 6-hydroxydopamine (6-OHDA) in rats. Beginning 60 days after 6-OHDA injection animals received a 14-day course of treatment with either the small molecule FKBP ligand GPI 1046 (10 mg/kg) or its vehicle alone. Striatal dopaminergic innervation density was determined from high power image analysis of striatal tyrosine hydroxylase (TH) immunohistochemistry. GPI 1046 treatment did not alter TH fiber density in the contralateral striatum but did produce significantly higher striatal TH fiber density in the ipsilateral caudate-putamen. This striatal re-innervation occurred in the absence of increased nigral sparing, and appears to reflect the GPI 1046 induced sprouting of residual TH+ fibers spared by the 6-OHDA lesion.
Ross
D T
DT
Department of Research, Guilford Pharmaceuticals, Baltimore, MD 21224, USA. ross_d@guilfordpharm.com
Guo
H
H
Howorth
P
P
Chen
Y
Y
Hamilton
G S
GS
Steiner
J P
JP
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008024:Ligands; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009412:Nerve Fibers / Q000201:enzymology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics; D022021:Tacrolimus Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
C104949:GPI 1046; D008024:Ligands; D011759:Pyrrolidines; D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D022021:Tacrolimus Binding Proteins