Curcumin improves learning and memory ability and its neuroprotective mechanism in mice.
BACKGROUND
Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer's disease (AD). Mitochondrial dysfunction has been implicated in this process of neuronal cell death. One promising approach for preventing AD is based upon anti-apoptosis to decrease death of nerve cells. In this study, we observed the memory improving properties of curcumin in mice and investigated the neuroprotective effect of curcumin in vitro and in vivo.


METHODS
The mice were given AlCl(3) orally and injections of D-galactose intraperitoneally for 90 days to establish the AD animal model. From day 45, the curcumin group was treated with curcumin for 45 days. Subsequently, the step-through test, neuropathological changes in the hippocampus and the expression of Bax and Bcl-2 were carried out to evaluate the effect of curcumin on the AD model mice. In cultured PC12 cells, AlCl(3) exposure induced apoptosis. The MTT assay was used to measure cell viabilities; flow cytometric analysis to survey the rate of cell apoptosis; DNA-binding fluorochrome Hoechst 33258 to observe nuclei changes in apoptotic cells and Western blot analysis of Bax, Bcl-2 to investigate the mechanisms by which curcumin protects cells from toxicity.


RESULTS
Curcumin significantly improved the memory ability of AD mice in the step-through test, as indicated by the reduced number of step-through errors (P < 0.05) and prolonged step-through latency (P < 0.05). Curcumin also attenuated the neuropathological changes in the hippocampus and inhibited apoptosis accompanied by an increase in Bcl-2 level (P < 0.05), but the activity of Bax did not change (P > 0.05). AlCl(3) significantly reduced the viability of PC12 cells (P < 0.01). Curcumin increased cell viability in the presence of AlCl(3) (P < 0.01). The rate of apoptosis decreased significantly in the curcumin group (P < 0.05) when measured by flow cytometric analysis. Curcumin protected cells by increasing Bcl-2 level (P < 0.05), but the level of Bax did not change (P > 0.05).


CONCLUSIONS
This study demonstrates that curcumin improves the memory ability of AD mice and inhibits apoptosis in cultured PC12 cells induced by AlCl(3). Its mechanism may involve enhancing the level of Bcl-2.
Pan
Rui
R
Department of Orthopedics, the First Affiliated Hospital, Medical College of Jinan University, Guangzhou, Guangdong, China.
Qiu
Sheng
S
Lu
Da-xiang
DX
Dong
Jun
J
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D007858:Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D017607:Aluminum Compounds; D002712:Chlorides; D018696:Neuroprotective Agents; D000077410:Aluminum Chloride; D003474:Curcumin