Guo_2011_Acta.Pharmacol.Sin_32_1446

AIM: To examine the protective effects of scutellarin (Scu) on rats with learning and memory deficit induced by beta-amyloid peptide (Abeta). METHODS: Fifty male Wistar rats were randomly divided into 5 groups: control, sham operation, Abeta, Abeta+Scu, and Abeta+piracetam groups. Abeta(25-35) was injected into the lateral ventricle (10 mug each side). Scu (10 mg/2 mL) or piracetam (10 mg/2 mL was intragastrically administered per day for 20 consecutive days following Abeta treatment. Learning and memory was assessed with Morris water maze test. The protein and mRNA levels of nicotinic acetylcholine receptor (nAChR) alpha4, alpha7, and beta2 subunits in the brain were examined using Western blotting and real-time PCR, respectively. The activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain and plasma were measured using Ellman's colorimetric method. RESULTS: In Abeta group, the escape latency period and first platform cross was significantly increased, and the total number of platform crossings was significantly decreased, as compared with the control and the sham operation groups. Both Scu and piracetam treatment significantly reduced the escape latency period and time to cross platform, and increased the number of platform crosses, but there were no significant differences between Abeta+Scu and Abeta+piracetam groups. In Abeta group, the protein levels of nAChR alpha4 and alpha7 subunits in the cerebral cortex were significantly decreased by 42%-47% and 58%-61%, respectively, as compared to the control and the sham operation groups. Scu treatment caused upregulation of alpha4 and alpha7 subunit proteins by around 24% and 30%, respectively, as compared to Abeta group, but there were no significant differences between Abeta+Scu and Abeta+piracetam groups. The protein level of nAChR beta2 subunit had no significant difference among different groups. The mRNA levels of nAChR alpha4, alpha7, and beta2 subunits were not significantly changed. In Abeta group, the activities of AChE and BuChE in the brain were significantly increased, but were significantly decreased in the plasma, as compared to the control and the sham operation groups. Scu or piracetam treatment restored the activities in brain and plasma nearly to the levels in the control group. CONCLUSION: The results suggest that Scu may rescue some of the deleterious effects of Abeta, possibly by stimulating nAChR protein translation and regulating cholinesterase activity.