Prevention of transneuronal degeneration of neurons in the substantia nigra reticulata by ablation of the subthalamic nucleus

Abstract

Transneuronal degeneration (TND) of neurons in the substantia nigra reticulata (SNR) occurs after initial ischemic or neurotoxin damage to the striatum. The mechanism is incompletely understood. In rats ibotenic acid (IBO) lesion of the caudate nucleus (CN) and the globus pallidus (GP) caused, 3 weeks later, a 47% loss of neurons (P < 0.001) in the SNR. Rats with IBO lesion confined to either the CN or the GP had SNR neuron numbers comparable to control. The volume of the SNR was decreased, as expected, in all groups with striatal lesions. To test whether the subthalamic nucleus (STN) played a role in the demise of SNR neurons, the STN was lesioned 1 week before animals were exposed to CN and GP injury. STN ablation prevented the expected SNR neuron loss. Based on the current information about basal ganglia anatomy, an imbalance between GABAergic and glutamatergic afferents may have caused TND in the SNR. These results suggest that the potential for the release of intrinsic excitotoxicity exists within certain anatomic networks.