Electrochemical And Histochemical Research On Neuroprotection Of Apomorphine On Parkinson's Disease

Previous studies have shown that R-Apomorphine (APO), the catechol - derived dopamine (DA) D1-D2 receptor agonist, has been shown to be the highly potent iron chelator and radical scavenger and inhibitor of membrane lipid peroxidantion. The present study was designed to investigate whether APO is neuroprotective in 6-OHDA unilateral lesioned rats. Using fast cyclic voltammetry (FCV), we monitored DA release evoked by electrical stimulation of medical forebrain bundle (MFB) from caudate putamen (CPu) of pretreatment the rats with APO followed by 6-OHDA unilateral lesion. High performance liquid chromatography electrical chemistry (HPLC-ECD) was used to detect the contents of DA and its metabolites dihydroxy- phenylacetic acid (DOPAC) and homovanillic (HVA). Tyrosine hydroxylase (TH) immuohistochemistry was employed to measure the numbers of TH immuoreactive neurons of substantia nigra zbna compacta (SNc) in order to examine the survival of dopaminergic neurons. Meanwhile, the changes of iron in SN was measured by Perls' iron staining.. The results were as follows:1. There was no significant difference of DA release in CPu between groups of APO (10mg/kg) and normal saline (NS ) treated in an hour.2. DA release in lesioned sides of 6-OHDA unilateral lesioned rats by pretreatment with intraperitoneal (i.p.) APO (10mg/kg) were apparently higher than that of NS treatment rats, while difference of DA release in unlesioned sides between groups of APO and NS pretreatment have no statistic significance.3. The contents of DA and HVA in lesioned sides of 6-OHDA unilateral lesioned rats by pretreatment with APO were significantly higher than NS treated rats, and nodifference compared with unlesioned sides.4. The numbers of TH immunoreactive neurons in SN of lesioned sides of 6-OHDA unilateral lesioned rats by pretreatment with APO were significantly higher than NS treated rats, and no difference compared with unlesioned sides.5. The SN of lesioned sides showed a decrease in iron staining density of pretreatment with APO on 6-OHDA unilateral rats in comparison with NS treated rats. There was no difference in iron staining of unlesioned sides between'two groups.These results suggested that APO was able to provide protection against 6-OHDA induced neurotoxicity by its protent iron chelator properties and free radical scavenger. Meanwhile, we examined that the neuroprotective property of APO was not due to its role of the DA D1-D2 receptor agnoist. The results provides experimental evidence for the clinical application of APO to prevent and treat Parkinson's disease (PD).Sun Yue (Physiology)Directed by Professor Xie Junxia...