| Parkinson's disease is a neurodegenerative disease of extrapyramid with a latent and slow procession. The pathological hallmarks of PD are reduction or loss of dopaminergic neurons in the mesencephalon and the presence of lewy bodies in altered neurons. The exact cause of the neuronal loss is still unknown. Hereditary basis can explain part of the pathogenesis. The cause of idiopathic and sporadic PD has focused on environmental exposures as causative agent. Epidemiological studies indicated that living in rural environment, farming, drinking well water, and occupational herbicide/pesticide exposure, especially the exposure of herbicide paraquat(PQ) and organochlorine insecticide dieldrin may have a certain relationship with PD. However none of them is confirmed to be Parkinsonogenic agent.PQ, bearing structural simility to the known dopaminergic neurotoxicant MPTP, has been suggested as a potential etiology factor in PD. Current studies showed that PQ elicite a distinct decrease in the level of dopamine(DA) of the dopamine terminals within the striatum. and induce the decrease in spontaneous motor activity.ES is one of organochlorine insecticide similar to dieldrin. It can cross the blood-brain barrier, and can induce the reduction of DA in rat brain. However there is little studies concerning the relationship betweenES and PD.Recently, an increasing body of evidence indicate that apoptosis may play a role in the pathogenesis of PD. Neurontoxins (MPP+,MPTP and 6-OHDA) can induce apoptosis in dopaminergic neurons in vivo and in vitro.The damage in substantia nigra dopamine system by PQ is firmed, but there is little study about the damage in ACh system. This study we try to elicite the effect on the ACh system and DA system of PQ and ES. The toxicity of ES to cultured PC 12 cells was detected by TURNEL staining and then the apoptosis ratio was assayed using FCM.At the same time, the change in ultrastructure of PC 12 cells was observed by transmission eletron micrograph.l.The effect of PQ and ES to DA system-ACh systemin the brain of PD animal modelsC57bl mice were randomely divided into 5 groups and were administered orally with PQ (5mg/kg,10mg/kg), ES(1.08mg/kg), MPTP (lOmg/kg) and normal saline perday. Sponteneous behavior was monitored. Two month later, after introveneous adminitration with 131I-QNBmAChR>99mTc-TRODAT-lDAI\ 125I-epideprideDAD2R imaging agent respectively, the brain tissues were sectioned and imaged by autoradiography. The levels of AChR, DAT and DAD2R were detected in the cortex (frontal, temporal, parietal, occipital) striatum, hyppocampus and thalamus. Results: The data indicated that the mice model of PD could be induced by PQ (10mg/kg), ES (1.08mg/kg) and MPTP (lOmg/kg) except for PQ (5mg/kg). Autoradiography indicated that there was nosignificant change in mAChR in the brain of PQ, ES and MPTP treated mice, comparing to the control group. DAT in striatum was significantly decreased in PQ (10mg/kg) treated mice. The specific radioactivity ratio of DAT was significantly decreased after exposure to PQ lOmg/kg (47.98% of control, PO.01); to ES 1.08mg/kg (79.80% of control, P<0.05);to MPTP lOmg/kg (70.71% of control, PO.01). The specific radioactivity ratio of DAD2R in striatum was significantly decreased after exposure to PQ lOmg/kg (60.61% of control, P<0.001); to ES 1.08mg/kg (61.04% of control, PO.001); to MPTP lOmg/kg (63.63% of control, P<0.001). These datas indicated that subchronically exposure to ES and PQ could induce the damage of DA system but has little effect on the ACh system in the brain of mice.2.The effect of ES on the proliferation and morphology of cultured PC12 cells.PC 12 cells were cultured in 6-well plates. The culture were treated with various concentration of toxins as follows: 1) MPP+(0.1,lmmol/L); 2) ES(0.01, 0.03, 0.06, 0.1mmol/L). After 24h of exposure to toxins, morphology of cells was observed and cells were collected for counting. The results showed that: PC 12 cells were significantly decreased after exposure to Immol/L MPP+(62.31... |
