| The Study on Parkinson's Disease Model by Stereotactic drug Injection in Rats |
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Hyung Ho Yoon, Joong Kee Min, Chong Sik Lee, Seong Who Kim, Onyou Hwang, Sang Ryong Jeon |
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Department of Neurological Surgery, Neurology, Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea |
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| Abstract |
Objective
It is necessary to develop methods producing animal model more efficiently for research of Parkinson’s disease (PD).
It is well known that 6-hydroxydopamine (6-OHDA) lesion model is appropriate for therapeutic studies. However, the coordinates
are variable according to the target and rat strains. The authors established methods to produce PD model with medial forebrain
bundle (MFB) lesion in Wistar rats and characterized the results by rotometer test, rota rod test, and histological evaluation.
Materials and Methods: Twelve male adult Wistar rats unilaterally received injection of saline into MFB in Sham group (n=6) and
6-OHDA in PD group (n=6) using stereotactic frame. After apomorphine (0.5mg/kg) was injected subcutaneously, rotation test was
performed to evaluate whether PD model was adequate. Rats showing more than 6 rotation per minute (RPM) within 30 minutes
were determined as successful PD model. Rota rod was used to test how motor function was changed following 6-OHDA lesion
and recognize whether this test is valid for 6-OHDA model in rat. Complete destruction of dopaminergic neurons was confirmed
by tyrosine hydroxylase (TH) immunostaining.
Results
All of the 6 rats in PD group rotated more than 6 RPM in apomorphine induced test. Rota rod test was not suitable for
evaluation of PD because rats had a tendency to fall off the rota rod randomly caused by huge differences of individual motor
function regardless of lesion or sham. TH immunostaining showed dopaminergic neurons decreased 91±3% at the lesion side of
substantia nigra in PD group.
Conclusion
The current study demonstrated that 6-OHDA injection into MFB using stereotactic frame is effective for producing
PD model in Wistar rats. This method for animal model will be applied to various therapeutic studies for PD. In addition, more
supportive evaluation methods for PD behavior are needed to be developed. |
| Key Words:
Animal model, Medial forebrain bundle, 6-hydroxydopamine, Tyrosine hydroxylase, Parkinson's disease, Wistar. |
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