Major histocompatibility complex expression in a rotenone model of Parkinson’s disease in rats

Abstract

Animal models can help determine the etiology of neurodegenerative diseases such as Parkinson's disease. Here, we conducted transcriptome analysis of the rotenone model of Parkinson's disease in rats. Exposure of 9-week-old Wistar rats to rotenone at 3 mg/kg/day for 14 days reduced spontaneous motor activity to 49% of that of control rats. Immunohistochemical analysis revealed increased expression of major histocompatibility complex (MHC) molecules in the substantia nigra of rotenonetreated rats, which was deduced by DNA array analysis. Further, gene set enrichment analysis of the transcriptome extracted the presence of a cytokine network, which included TNF-α. The expression of these proteins tended to be reduced at developed states of the disease. Thus, our analyses of the rotenone rat model still provides new insights into the etiology of Parkinson's disease.

The temporal turning window for rat behavioral phenotypes by rotenone

“…As mentioned above, rotenone has been shown to be a dopaminergic toxin, developing Parkinson's disease with adult rats (Betarbet et al, 2000;Ishido and Shimaya, 2016) and we demonstrated that exposure of rat pups to rotenone causes hyperactivity during juvenile and adulthood due to dopaminergic lesions by rotenone (Ishido et al, 2017).…”

“…Thus, spontaneous motor activity of these two kinds of animal models could be quantitative index. We employed Supermex® system to measure spontaneous motor activity, as described previously ( Masuo et al ., 1997( Masuo et al ., , 2007Masuo and Ishido, 2011 ;Ishido et al ., , 2004cIshido et al ., , 2004dIshido et al ., , 2005Ishido et al ., , 2017Ishido and Shimaya, 2016 ). A Supermex® sensor head comprising paired infrared pyroelectric detectors was used to measure the radiated body heat of each animal.…”

“…To compare the transcriptome of rat hyperactivity dis- Adapted from ref. Shimaya, 2016 andIshido et al, 2017. Table 1.…”

“…1.9 Protein kinase C delta 1.4 Leukocyte immunoglobulin-like receptor 1.2 Dehydrogenase/reductase member7 1.0 Decrement Chemokine receptor 3 -5.3 Insulin-like growth factor binding protein 5 -3.6 Tenascin N -3.2 sulfotransferase -3.1 p53-like inducible protein -2.7 WNT1 inducible protein -2.6 Sarcospan -1.5 Anaphase promoting complex subunit1 -1.4 Heat shock protein 70 -1.3 Calcitonin receptor-like -1.2 RING finger protein Abhydrolase domain containing 6 -1 Kuppel-like factor2 -1 Adapted from ref. Ishido et al, 2017. orders in this study, we created the rotenone model of Parkinson's disease (Greene et al, 2010;Greene, 2012;Ishido and Shimaya, 2016). Total RNA was isolated from the midbrain of 11-week-old rats and then transcribed to cDNA.…”