Glial cell line-derived neurotrophic factor protects midbrain dopamine neurons from the lethal action of the weaver gene: a quantitative immunocytochemical study.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect and repair midbrain dopamine neurons in vivo using animal models created with neurotoxins. The weaver mouse (wv/wv) has natural and spontaneous midbrain dopaminergic cell death which gives a unique opportunity to examine the effects of GDNF. The present study was designed to investigate a possible neuroprotective role by GDNF for midbrain dopamine neurons in the wv/wv. Weaver pups were given 1 microl injections on postnatal day 1. The wv/wv placebo group received a single unilateral injection into the right lateral ventricle of phosphate buffered saline (PBS) while the GDNF treated wv/wv mice received either 1.0 microg/microl or 10.0 microg/microl GDNF in PBS. All mice were sacrificed on postnatal day 20 and their brains were processed for tyrosine hydoxylase (TH) immunocytochemistry. When compared to the placebo group, the 1 microg GDNF group showed significantly less cell death on the injection side, but the contralateral side showed no significant sparing of TH neurons. The combined counts from both sides show significantly more TH staining neurons in the 1 microg GDNF group compared to placebo. When compared to placebo-injected controls, the 10 microg GDNF treated group showed significantly more TH staining neurons on the injected side, contralateral side, and combined. The results demonstrate that GDNF does protect weaver dopaminergic midbrain neurons from the lethal action of the weaver gene and the effect is positively correlated to dosage.
Broome
J D
JD
Department of Medical Neurobiology, Indiana University, Indianapolis, IN 46202, USA.
Wills
K V
KV
Lapchak
P A
PA
Ghetti
B
B
Camp
L L
LL
Bayer
S A
SA
D000818:Animals; D002452:Cell Count; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005804:Genes, Lethal; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine