Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia

BMC Neuroscience

Bryce Vissel¹  Sandy Stayte¹  Gary P. Morris¹  Peggy Rentsch² 

[1] Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney;Faculty of Medicine, University of New South Wales;

关键词: Abnormal involuntary movements;    Neuroinflammation;    Parkinson’s disease;    Stereology;    Striatum;    Substantia nigra pars compacta;   

DOI  :  10.1186/s12868-019-0487-7

来源: DOAJ

【 摘 要 】

Abstract Background Accurately assessing promising therapeutic interventions for human diseases depends, in part, on the reproducibility of preclinical disease models. With the development of transgenic mice, the rapid adaptation of a 6-OHDA mouse model of Parkinson’s disease that was originally described for the use in rats has come with a lack of a comprehensive characterization of lesion progression. In this study we therefore first characterised the time course of neurodegeneration in the substantia nigra pars compacta and striatum over a 4 week period following 6-OHDA injection into the medial forebrain bundle of mice. We then utilised the model to assess the anti-dyskinetic efficacy of recombinant activin A, a putative neuroprotectant and anti-inflammatory that is endogenously upregulated during the course of Parkinson’s disease. Results We found that degeneration of fibers in the striatum was fully established within 1 week following 6-OHDA administration, but that the loss of neurons continued to progress over time, becoming fully established 3 weeks after the 6-OHDA injection. In assessing the anti-dyskinetic efficacy of activin A using this model we found that treatment with activin A did not significantly reduce the severity, or delay the time-of-onset, of dyskinesia. Conclusion First, the current study concludes that a 3 week duration is required to establish a complete lesion of the nigrostriatal tract following 6-OHDA injection into the medial forebrain bundle of mice. Second, we found that activin A was not anti-dyskinetic in this model.

【 授权许可】

Unknown