The Effects Of VMAT2 Gene Combined With Environmental Toxin On Non Motor Symptoms Of Parkinson's Disease

Objective: By observing the abnormal behaviours of the C57BL/6 mice and the expression of monoamine neurotransmitters of brain, we analyze the effects of VMAT2 gene combined with environmental toxin on non motor symptoms of Parkinson's disease.Methods: Male and adult wildtype C57BL/6 mice(almost 12 months old) were randomly divided into 2 groups for control and rotenone group. Mice in the control group were intragastric administrated with vehicle(corn oil). Mice in the rotenone group were intragastric administrated with rotenone. The other VMAT2(+/-) mice expressing 50% VMAT2 activity were randomly divided into 2 groups for VMAT2(+/-) and VMAT2(+/-) + rotenone group. Mice in the VMAT2(+/-) group were intragastric administrated with vehicle(corn oil). Mice in the VMAT2( +/-) + rotenone group were intragastric administrated with rotenone. After 4 months, we observe the consumption test of sucrose and tail suspension test, to evaluate the depression degree of these mice. Then HPLC was used to measured the contents of DA, 5-HT, NE, DOPAC, HVA in the brains of these mice.Results: Consumption test of sucrose solution: The preference of sucrose in the WT+Rot group and the VMAT2(+/-)group and the VMAT2(+/-)+Rot group are lower than that in the WT group(p<0.05). The preference of sucrose in the VMAT2(+/-)+Rot group is lower than that in the VMAT2(+/-)group(p<0.05).Tail suspension test: The immobility time in the WT+Rot group and the VMAT2(+/-) group and the VMAT2(+/-)+Rot group is longer than that in the WT group(p<0.05). The immobility time in the VMAT2(+/-)+Rot group is longer than that in the VMAT2(+/-)group(p<0.05).HPLC: The contents of DA, 5-HT and NE in the WT+Rot group and the VMAT2(+/-)group and the VMAT2(+/-)+Rot group have significantly decreased than those monoamine neurotransmitters in the WT group(p<0.05). The contents of DA, 5-HT and NE in the VMAT2(+/-)+Rot group are also significantly lower than those in the VMAT2(+/-)group(p<0.05).Conclusion: 1. By observing the behaviouristics of the mice, we found that rotenone can not only induce the motor symptoms of Parkinson's disease, but also can induce non motor symptoms. Depression exists in the VMAT2 heterozygote mice. VMAT2 gene knockdown can induce non motor symptoms in PD. VMAT2 gene plays a protective role in Parkinson's disease.2. VMAT2 gene knockdown combined with rotenone could better simulate non motor symptoms by regulating contents of monoamine neurotransmitters in PD.