Subthalamic nucleus lesion in rats prevents dopaminergic nigral neuron degeneration after striatal 6-OHDA injection: behavioural and immunohistochemical studies.
Several studies have shown that antagonists of N-methyl-D-aspartate receptors provide protection of the dopaminergic nigrostriatal pathway in animal models of Parkinson's disease. Since the substantia nigra compacta receives a moderate glutamatergic innervation from the subthalamic nucleus, we tried to determine whether subthalamic nucleus lesion could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Experiments were carried out on four groups of rats. Group 1 (n = 10) received a unilateral injection of 6-hydroxydopamine in the striatum and group 2 (n = 10) received kainic acid in the subthalamic nucleus. Group 3 (n = 10) received an injection of kainic acid in the subthalamic nucleus and 1 week later an injection of 6-OHDA in the striatum. Group 4 (n = 5) received the same treatment but kainic acid was replaced by saline. Apomorphine induced an ipsilateral rotation in rats of groups 2 and 3 and a contralateral rotation in rats of groups 1 and 4. The number of tyrosine hydroxylase-immunoreactive cells in the pars compacta of the substantia nigra was not significantly decreased on the side ipsilateral to 6-OHDA striatal injection in rats of groups 1 and 4. These results show that subthalamic nucleus lesion provides neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity and opens a new way for slowing or stopping the progression of Parkinson's disease.
Piallat
B
B
Laboratoire de Neurobiologie Préclinique, INSERM U.318, CHU, Pavillon B, BP 217, 38043 Grenoble Cedex 09, France.
Benazzouz
A
A
Benabid
A L
AL
D000818:Animals; D004298:Dopamine / Q000032:analysis*; D004334:Drug Administration Schedule; D007839:Functional Laterality; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009410:Nerve Degeneration / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D013787:Thalamic Nuclei / Q000502:physiology*
D016627:Oxidopamine; D007608:Kainic Acid; D004298:Dopamine