Journal of the Korean Society of Stereotactic and Functional Neurosurgery 2011;7(1):6-11.
Published online June 30, 2011.
The Study on Parkinson's Disease Model by Stereotactic drug Injection in Rats
Hyung Ho Yoon, Joong Kee Min, Chong Sik Lee, Seong Who Kim, Onyou Hwang, Sang Ryong Jeon
Department of Neurological Surgery, Neurology, Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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.
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.
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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