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 protec t and repair midbrain dopamine neurons in vivo using animal models created with neurotoxins. The weaver mouse (wu/wu) has natural and spontaneous midb rain dopaminergic cell death which gives a unique opportunity to examine th e effects of GDNF. The present study was designed to investigate a possible neuroprotective role by GDNF for midbrain dopamine neurons in the wu/wu. W eaver pups were given 1 mu l injections on postnatal day 1. The wu/wu place bo group received a single unilateral injection into the right lateral vent ricle of phosphate buffered saline (PBS) while the GDNF treated wu/wu mice received either 1.0 mu g/mu l or 10.0 mu g/mu l 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, t he 1 mu g GDNF group showed significantly less cell death on the injection side, but the contralateral side showed no significant sparing of TH neuron s. The combined counts from both sides show significantly more TH staining neurons in the 1 mu g GDNF group compared to placebo. When compared to plac ebo-injected controls, the 10 mu g GDNF treated group showed significantly more TH staining neurons on the injected side, contralateral side, and comb ined. The results demonstrate that GDNF does protect weaver dopaminergic mi dbrain neurons from the lethal action of the weaver gene and the effect is positively correlated to dosage. (C) 1999 Elsevier Science B.V. All rights reserved.