Effect Of Chronic Episodic Hypoxia On Behavior And Striatal Dopamine Content In Mice Of Parkinson Disease Model

Object:By observing the effect of chronic episodic hypoxia(EHYP) on behavior and content of dopamine(DA) in striatum in mice of Parkinson disease(PD) model, we want to study the effect sleep apnea syndrome(SAS) could have on PD itself i.e. on nigrostriatal dopaminergic system in patients with PD.Methods:First we set up a chronic episodic hypoxia mouse model.We designed a box used to cause hypoxia by ourselves which can be closed tightly .The open and closure of the box was controlled by a autovalve which made the open to give oxygen and the closure to cause hypoxia recycle automaticly and chronic episodic hypoxia can be made by this.Then we chose 44 male C57BL/6 mice that were 6 weeks old and divided them into four groups: paraquat(PQ)+EHYP group, EHYP group, paraquat group and control group.There were 11 mice in every group. The C57BL/6 mice in PQ+EHYP group were exposed to paraquat (10 mg/kg), with the drugs being injected intraperitoneally.And after paraquat was injected for 2 weeks,EHYP was given too,8 h every day.The C57BL/6 mice in EHYP group were given the same volume saline by intraperitoneal injection twice a week for 6 weeks and EHYP was given the same as PQ+EHYP group. The C57BL/6 mice in PQ group was injected paraquat the same as PQ+EHYP group but not given EHYP. The C57BL/6 mice in control group were given the same volume saline by intraperitoneal injection and were not given EHYP.In the end,after the last injection(paraquat or saline) for 1 week, the behavior of the mice in all groups was examined by observing spontaneous behavior and appling behavior tests,including mounting test,swimming test and gait test and the content of DA in striatum was determined by high performance liquid chromatography and ultraviolet detection after behavior test was over the second day.Results:C57BL/6 mice in paraquat+EHYP group showed Parkinsonism(reductions in locomotor activity and motor coordination and bradykinesia).Excepted that no significant difference was found in gait test in all groups,the C57BL/6 mice in paraquat+EHYP group showed the worst performance with the lowest score on mounting test and swimming test,different significantly with the mice in the other groups (paraquat group,EHYP group and control group)(P<0.05) and and showed obvious decrease in the content of DA in striatum compared with the mice in the other groups(P<0.01).No significant difference was found in behavior tests and the content of DA in striatum within the other groups(P>0.05).Conclusion:EHYP combined with paraquat can cause Parkinsonism and obvious decrease in the content of DA in striatum in C57BL/6 mice,can make more serious damage to nigrostriatal dopaminergic system in C57BL/6 mice. EHYP combined with paraquat can strengthen the damage to nigrostriatal dopaminergic system obviously compared with PQ alone.The reason why EHYP combined with PQ can make much stronger damage to nigrostriatal dopaminergic system,could be the insult effects on nigrostriatal dopaminergic system were made synergistically by EHYP and PQ. The exact reason need to be studied further.