Curcumin Improves Learning And Memory Ability And Its Neuroprotective Mechanism In Mice

ObjectiveTo observe the memory-improving properties of curcumin in mice and investigate theneuroprotective effect of curcumin in vitro and vivo.Methods(1) The memory impairment mice were induced by scopolamine. Step down test andMorris water maze test were used to observe the learning and memory ability in curcumintreated mice. Biochemical assessments of ACHE, MDA, and GSH-Px levels in brains weremeasured.(2) The mice were orally administrated with AlCl₃ and ip injection of D-galactose for 90days to set up AD animal model. From day 45, curcumin group was treated with middle dosecurcumin which was the most effective dose tested. The curcumin treatment continued for 45days. Subsequently, the step-through test, neuropathological changes in hippocampal and theexpression of Bax and Bcl-2 were carried out to evaluate the effect of curcumin on the ADmodel mice.(3) In cultured PC12 cells, AlCl₃ exposure induced apoptosis. MTT assay to measurethe cell viabilities; flow sytometric analysis to survey the rate of cell apoptosis;DNA-binding fluorochrome Hoechst 33258 to observe nuclei changes in apoptosis cells andWestern blotting analysis of Bax, Bcl-2 activities to investigate the mechanisms by whichcurcumin protect cells from toxicity.Results(1) Oral administration of curcumin significantly reduced the numbers of step-downerrors (P＜0.05), prolonged the step-down latency (P＜0.05) induced by scopolamine. InMorris water maze test, mice treated with curcumin showed a remarkably reduced escapelatency time compared to those in the scopolamine group (P＜0.05). After the platform wasremoved, the total time the mice swan in the target quadrant was also remarkably higher inthe curcumin group than model group (P＜0.05). The data also suggest that curcumin significantly inhibited AChE activity (P＜0.01) and prevented oxidative stress characterizedby the significant reduction in MDA content and the increased GSH-Px activities in the brain(P＜0.01).(2) Middle dose of curcumin significantly improved the memory ability of AD mice instep-through test, featured by reduced the number of step-through errors (P＜0.05),prolonged step-through latency (P＜0.05). Curcumin also attenuated the neuropathologicalchanges in hippocampus and inhibit apoptosis accompanied by an increase in Bcl-2 activity(P＜0.05), but the activity of Bax didn't change (P＞0.05).(3) AlCl₃ significant reduced the viability of PC12 cells (P＜0.01). Low and middledose of curcumin can increased cell viability induced by AlCl₃ (P＜0.01). The rate ofapoptosis decreased significantly in curcumin group (P＜0.05), which were measured byflow sytometric analysis. Curcumin protected cells by increasing Bcl-2 activity (P＜0.05)butthe activity of Bax didn't change (P＞0.05)Conclusions(1) Our results suggest that curcumin can induce cognitive improvement by enhancingthe cholinergic system and its antioxidant activity.(2) Curcumin improves the memory ability of AD mice. Its mechanism may involved inanti-apoptosis featured by promote the activation of Bcl-2.(3) Curcumin inhibits apoptosis in cultured PC12 cells induced by AlCl₃. Its mechanismmay be involved in enhancing the activation of Bcl-2.