Hyperphosphorylation of protein Tau in hippocampus may cause cognitive dysfunction of propofol-anesthetized rats

H.-B. Zheng, Y.-T. Fu, G. Wang, L.-H. Sun, Y.-Y. Fan, T.-W. Yang

Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, China. Yantaofu@163.com

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• Pharmacology

OBJECTIVE: We aimed to explore the effect of hyperphosphorylation of Tau on cognitive function of propofol-anesthetized rats.

MATERIALS AND METHODS: Thirty 2-month-old male Wistar rats weighing 180-220 g were randomly divided into 3 groups (n=10): group of treating with saline (C group), group of treating with propofol for 1 hour (P1) and 24 h (P24 group). The cognitive function of rats was tested by Morris water maze before and 1 h or 24 h after drug administration. The rats were then sacrificed. The protein and mRNA expression levels of GSK-3β, total and phosphorylated Tau, cyclin D1, p27kip1 and c-caspase 3 in hippocampus were determined by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively.

RESULTS: Compared with group C, the incubation period of P1 group and P24 group was prolonged, and the target quadrant retention time was shortened (p<0.05). There was no statistical difference between P1 and P24 group (p>0.05). Immunohistochemistry showed that compared with group C, p-Tau in hippocampus of P1 group and P24 group was highly expressed, with statistical difference (p<0.05). Western blot and RT-PCR showed that protein and mRNA expressions of GSK-3β, phosphorylated Tau, cyclin D1 and c-caspase 3 in hippocampus of P1 and P24 groups were up-regulated (p<0.05).

CONCLUSIONS: Propofol-induced cognitive dysfunction in rats may be related to the hyperphosphorylation of Tau that causes neuronal cells to re-enter the cell cycle, thus leading to apoptosis.

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