| Objective : To investigate the relationship between changes of dopamine transporter in the ventral tegmental area(VTA)and cognitive dysfunction in elderly rats after surgery.Methods:Eighty male SD rats,aged 18-20 months,had a body mass of 300-500 g.They were randomly divided into 8 groups: Normal group(N),Sham group(S),model 3-day group(PND,P3),model 7-day group(PND,P7),virus 3-day group(AAV3),virus 7-day group(AAV7),negative virus 3-day group(NC3),and negative virus 7-day group(NC7).Morris water maze and conditioned fear experiment were used to judge the degree of cognitive impairment in rats.Immunofluorescence staining was performed to observe the protein location and expression of DAT,α-synuclein(α-syn)and β-Amyloid1-42(Aβ1-42)in the VTA region and the hippocampal CA1 region,and the protein content of α-syn and Aβ1-42 was detected by Western blot,and the protein content differences among the groups were compared.Results:In the behavioral test,compared with the N group,the rats showed significant cognitive decline 3and 7 days after surgery.In the Morris water maze experiment,the residence time in the target quadrant and The Times of crossing the target platform of the elderly rats were significantly reduced 3 and 7 days after surgery compared with the preoperative ones(P<0.05),and the escape incubation period was significantly longer than that before operation(P<0.05),and after knocking down the dopamine transporter in the VTA region,the cognitive decline of the elderly rats was significantly improved;In the conditional fear test,it was found that the fear memory ability of the elderly rats for the scene decreased significantly 3and 7 days after surgery(P<0.05),3 days after surgery,the fear memory of sound decreased compared with that before surgery(P<0.05)and recovered to the preoperative level 7 days after operation(P>0.05),knockdown of dopamine transporter in VTA region can improve the impairment of memory function in rats;Immunofluorescence and WB results showed that compared with the N group,the contents of α-synuclein and β-amyloid1-42 protein in hippocampal CA1 region of the aged rats were significantly increased at 3days and 7 days after surgery(P<0.05);After knockdown of dopamine transporter in VTA region,the contents of α-synuclein and β-amyloid1-42 in hippocampal CA1 region were significantly lower than those in surgery group(P<0.05).Conclusion : Dopamine transporter in VTA region is involved in cognitive dysfunction induced by anesthesia surgery in elderly rats,and the effect of DAT changes in VTA region on postoperative cognitive function in elderly rats may be related to the regulation of α-syn and Aβ1-42 protein aggregation in hippocampus. |
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