Background: Parkinson's disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer's disease and is very often accompanied by the lower urinary tract symptoms. Bladder ischemia reperfusion injury (I/R injury) is a common factor contributing to age-related structural and functional changes of the bladder therefore has been shown to be important in the pathogenesis of the lower urinary tract. However, there are very few studies on PD with other voiding dysfuction, especially with I/R injury. The purpose of this study was to examine bladder wall changes after I/R injury in the PD using transgenic dog model.
Material and methods: The 4 PD transgenic beagles were divided into two groups (I/R, sham-operated group) of 2 dogs each. The I/R injury was induced by clamping both cranial vesical arteries and caudal vesical arteries for 2 hrs and declamping for 7 days. Western blot assay was perfomed to evaluate MAPK pathway, NF-kB, NGF, NRG1 and muscarinic acetylcholine receptors (M1, M3) of harvested bladder. The intensities of caspase-3, M1 and M3 expression at the bladder were analyzed using the confocal microscope and image analyzer.
Results: In the I/R injury group, caspase-3, JNK-1, p38 (pro-apoptotic kinase) showed significantly higher expression whereas lower expression of Erk1 (anti-apoptotic kinase) than sham op group. (p<0.05) I/R injury induced bladder apoptosis is associated with an imbalance in the MAPK pathways. NF-kB expression was significantly increased in the I/R group than the sham-op group. (p<0.05) NGF and NRG1 expression were significantly increased in the I/R group than the sham-op group. (p<0.05) M1 and M3 expression were significantly increased in the I/R group than the sham-op group. (p<0.05)
Conclusions: This study was conducted by using a cloned dog with overexpressing the hDJ-1 gene transgenic Parkinson's disease for the first time. The results are similar to in human Parkinson's disease because of sharing disease pathophysiology more similar to humans than in existing rodent models. In this study. I/R injury in the Parkinson's disease model causes exacerbation of apoptosis and inflammatory change. This exacerbates detrusor hyperactivity and, if I/R injury persists or repeats, detrusor underactivity or detrusor areflex may occur. However all these bladder changes in the parkinson's disease are thought to be lesser than the changes in the normal control group.