Effects of different doses of 6-OHDA on dopaminergic neurons and be-haviors in mice
10.3969/j.issn.1000-4718.2024.11.003
- VernacularTitle:不同剂量6-OHDA对小鼠多巴胺能神经元及行为的影响
- Author:
Yue WU
1
;
Lidi LU
;
Tao QING
;
Qingyue JIANG
;
Suxin SHI
;
Yanzhu FAN
;
Guangzhan FANG
Author Information
1. 中国科学院成都生物研究所,四川 成都 610213;中国科学院大学,北京 101408
- Keywords:
Parkinson disease;
6-hydroxydopamine;
substantia nigra pars compacta;
corpus striatum;
dyskinesia
- From:
Chinese Journal of Pathophysiology
2024;40(11):2005-2013
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the relationship between the number of dopaminergic neurons and the locomo-tor behavior of animals,and to provide a reference basis for the modeling of mice with different stages of Parkinson disease(PD)and different types of locomotor deficits based on 6-hydroxydopamine(6-OHDA)injection.METHODS:We in-duced lesions in the substantia nigra pars compacta(SNc)by administering various doses of 6-OHDA(3 g/L,6 g/L,and 12 g/L)to create PD mouse models with differing degrees of injury,thereby mimicking the various stages of PD progression observed in patients(early,moderate and advanced stages).On the 14th day post-surgery,we evaluated the behavioral deficits of the mouse models using the rotarod test,pole test,beam traversal test,open field test,and gait analysis.Fur-thermore,the quantification of tyrosine hydroxylase(TH)-positive neurons within the SNc and TH-stained dopaminergic terminals in the corpus striatum caudate-putamen(CPu)was conducted utilizing immunofluorescence staining techniques to assess brain tissue damage.RESULTS:Compared to the control group,the number of dopaminergic neurons in the SNc was significantly reduced in both the high-dose group(P<0.05)and the medium-dose group(P<0.05)following 6-OHDA injection,demonstrating a dose-dependent effect(Spearman correlation,P<0.01).Similarly,the dopaminergic terminals in the CPu were significantly diminished in the high-dose group(P<0.01)and the medium-dose group(P<0.05).Behavioral tests revealed that mice in the high-dose group exhibited severe impairments in motor coordination and hindlimb balance,as evidenced by reduced rotarod test times,gait abnormalities,and asymmetrical forelimb use in the cylinder test.In contrast,mice in the medium-and low-dose groups displayed only mild declines in limb coordination,while their autonomous motor abilities and gait indices remained largely unaffected.CONCLUSION:The results reveal a dose-dependent effect on dopamine neuron damage,with higher doses causing the severest damage.Unexpectedly,signifi-cant locomotion impairments were only manifested in the high-dose group.This suggests that a mouse model induced by higher 6-OHDA dose is effective for studying PD and associated dyskinesia.Conversely,animal models with low to medi-um doses can be useful for exploring the early stages of PD locomotion symptoms.
