Effect Of Exposure Of Paraquat, Maneb And Rotenone On The System Of Substantial Nigra And Striatum In Mice

As a common neurodegeneration disease, the relationship between the etiology of parkinson's disease (PD) and environmental factors was extremely closed. The related researches had indicated that environmental toxins, including pesticides, had been playing an important role in inducing the onset of PD. Some studies had involved that paraquat and rotenone are related with the emerging of PD, but most of the results were obtained from epidemiology investigation. At the same time, the results coming from the exposure of experimental animals were not always consistent. Moreover, the previous researches had been mainly focusing on the observations of one single pesticide's neurotoxicity, less on the combinational effects of paraquat and rotenone. The present research investigated the neurotoxicity produced by three typical pesticides (rotenone, paraquat and maneb) in mice after chronic exposure of any kind of the three pesticides or paraquat combined with maneb or rotenone in low dose. These neurotoxicity investigations in mice include animal behaviors, histopathology of substantia nigra compact, and the dopamine concentration in striatum (CPu).The main results are as follows:1. After alone exposure of lower paraquat (5mg/kg) or maneb(15mg/kg) for 16 weeks, the number and morphology of DA-ergic neurons in SNc area of mice did not change compared to the control animals, animal behaviors and DA concentration in CPu did not change either. However, after combinational exposure of paraquat or maneb with same dosage for 8weeks or 16weeks, DA-ergic neurons in animal SNc lost 25% or 40% respectively, the cell in substantial nigra presented progressive degenation.2. After alone exposure of higher paraquat (8mg/kg) or rotenone (1.0mg/kg) for 12 weeks, it was shown significant lesions of DA-ergic neurons in SNc and significant neural loss of 26% or 15% in SNc respectively. Although the DA concentration in CPu of these paraquat exposure mice do not decline obviously, the time of pole test was prolonged significantly compared with control group, which showed that the locomotory capacity of animals had impaired. The DA concentration in CPu of the rotenone-exposure group decreased by 24%, and the times of crossing grids decreased significantly, all of these could indicate obviously strong neurotoxicity of rotenone.3. Combinational exposure with paraquat (8mg/kg) and rotenone for 12 weeks, could induce mice serious impairments in SNc. Very significant cell loss of 33% was observed in SNc. The DA concentration in CPu decreased by 35% in this group. The results were consistant with behavirol tests, which showed that the times of crossing grids decreased significantly, and the time of pole test prolonged significantly.These results above suggested that:1. Both rotenone and paraquat had the neurotoxicity of inducing PD. Exposure of rotenone or paraquat could result in the impairment or loss of DA-ergic neurons in SNc, the declining of DA concentration in CPu, and the impairment of locomotory capacity.2. The neurotoxicity of paraquat presented the certain degree dose-response relationship. The certain time-response effect could be obsvered in both single or united exposure group. These indicated that the environmental factors could have thresholds of time or dose in inducing PD.3. The synergistic neurotoxicity effects could be observed in either combination of paraquat and maneb, or that of paraquat and rotenone. Their combiational exposure could induce more serious impairment of the SNc-CPu system than the single exposure. It indicated that the cooperation effect of two or more than two kinds of toxicants could be the important inducing factors of PD's pathogenesis.It was observed the effects of chronic neurotoxiticy effect of paraquat, maneb and rotenone in the present study. The neurotoxicity investigation included ethology, pathology and neurochemistry involved with PD. It was found that paraquat combined choronic exposure with rotenone in low-dose could induce parkinsonism-like behaviors in experimental mice. This behavioral symptom was caused by the pathology changes in SNc-CPu pathway. Our results would provide references for environmental etiology of PD, and provide basis for related hygiene precaution.