Prevention of neurotoxin damage of 6-OHDA to dopaminergic nigral neuron by subthalamic nucleus lesions.
OBJECTIVE
To investigate the possibility that subthalamic nucleus (STN) ablation could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA).


METHODS
Sixty rats were divided into 6 groups (n = 10). The control group received a unilateral microinjection of 6-OHDA into the right ventral tegmental area (VTA) and the right median forebrain bundle (MFB). Group 1 received an administration of kainic acid (KA) into the right STN and, 1-week later, an injection of 6-OHDA in the right VTA and MFB. Groups 2-5 received an injection of 6-OHDA in the right VTA and MFB, 1 h, 2 h, 3 days, and 7 days before KA in the right STN respectively. Four weeks later, the changes of tyrosine hydroxylase (TH)-positive (dopaminergic) neurons in the SNc were investigated with immunocytochemical and morphometrical methods.


RESULTS
The number of TH-positive cells in the SNc on the injected side of treated groups (groups 1-5) and control group were 71.46 +/- 6.84, 57.07 +/- 5.54, 51.09 +/- 4.85, 12.68 +/- 2.67, 4.15 +/- 1.60 and 3.40 +/- 1.54/slice, which decreased to 96.7, 72.9, 69.8, 17.2, 5.6 and 4.4% of the non-injected side, respectively. The number of TH-positive neurons in groups 1-4 significantly increased in comparison with the controls (p < 0.05, 0.01). In group 5, there were no remarkable differences in contrast to the number of TH-positive neurons of the controls (p > 0.05). The difference in the number of TH-positive neurons between groups 1-5 was statistically significant (p < 0.01).


CONCLUSIONS
The results indicate that STN ablation can provide antiglutamate-based neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity.
Chen
L
L
Department of Neurosurgery, Navy General Hospital of PLA, Beijing, China. chenlin_China@sina.com
Liu
Z
Z
Tian
Z
Z
Wang
Y
Y
Li
S
S
D000344:Afferent Pathways / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004298:Dopamine / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D018698:Glutamic Acid / Q000502:physiology; D007608:Kainic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D008845:Microinjections; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000473:pathology*; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D017557:Ventral Tegmental Area / Q000187:drug effects
D015415:Biomarkers; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D018698:Glutamic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D007608:Kainic Acid; D004298:Dopamine