Ablation of the subthalamic nucleus supports the survival of nigral dopaminergic neurons after nigrostriatal lesions induced by the mitochondrial toxin 3-nitropropionic acid

We investigated the role of the excitatory afferents from the subthalamic n ucleus (STN) in the death of nigral dopamine (DA) neurons after nigrostriat al axon terminal lesions. Nigral DA neurons were detected by use of both ty rosine hydroxylase immunolabeling or retrograde labeling of nigral cells wi th fluorogold. Sprague-Dawley rats were subjected to unilateral, quinolinic acid-induced destruction of the STN. Sham lesions of the STN were made by injecting phosphate-buffered saline. Two weeks after STN ablation, lesions of nigrostriatal DA neurons were induced by intrastriatal injections of eit her the mitochondrial toxin 3-nitropropionic acid (3-NP) or the catecholami ne toxin 6-hydroxydopamine (6-OHDA). Intrastriatal injections of 3-NP, or 6 -OHDA caused a progressive loss of nigral tyrosine hydroxylase-positive or fluorogold-labeled DA neurons in a dose-dependent manner. Previous ablation of the STN significantly attenuates the loss of DA neurons in rats receivi ng 3-NP but not 6-OHDA. Sham lesions of the STN did not affect DA neuron de ath induced by the toxins. The results indicate that the excitatory inputs from the STN may contribute to the death of nigral DA neurons under a condi tion of 3-NP-induced metabolic impairment.