GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR SUSTAINS AXOTOMIZED BASALFOREBRAIN CHOLINERGIC NEURONS IN-VIVO - DOSE-RESPONSE COMPARISON TO NERVE GROWTH-FACTOR AND BRAIN-DERIVED NEUROTROPHIC FACTOR

Glial cell line-derived neurotrophic factor (GDNF) was infused continu ously for 2 weeks into the ventricles of male Wistar rats that had rec eived a unilateral knife transection of the fimbria/fornix. In vehicle -treated, control animals, there was a 70% loss of choline acetyltrans ferase (ChAT)-positive and a 60% loss of p75-positive neurons in the s eptum/diagonal band ipsilateral to the axotomy as identified by immuno histochemistry, with no loss in ChAT biochemical activity. GDNF treatm ent at 10 mu g/day completely prevented the loss of p75-positive neuro ns, significantly reduced the loss of ChAT-positive neurons to 40% of normal, and stimulated ChAT biochemical activity to 40% more than norm al in an axotomy-dependent manner. GDNF is I order of magnitude less p otent than NGF but, unlike NGF, had little or no effect on normal, uni njured neurons. GDNF was 1 order of magnitude more potent than BDNF, a nd BDNF had no effect on ChAT biochemical activity. GDNF and NGF inhib ited weight gain, whereas BDNF induced significant weight loss and dea th at the dosage of 100 mu g/day.