[Effect of curcumin on hippocampal IRS-1 and p-IRS-1 expressions in APP/PS1 double transgenic mice].
OBJECTIVE
To observe the effect of curcumin on the expressions of insulin receptor substrate-1 (IRS-1) and phosphated insulin receptor substrate-1 (p-IRS-1I) in APP/PS1 double transgenic mice of the AD model.


METHODS
Three-month-old APP/ PSI double transgenic mice were randomly divided into the model group, the positive rosiglitazone control group and curcumin high (400 mg . kg-1 . d-1), medium (200 mg . kg-1 . d-1) and low (100 mg . kg-1 . d-1) dose groups. The normal group was composed of non-transgenic mice under the same background. After they were orally administered for three months, they were detected with immunohistochemistry, Western blot and RT-PCR.


RESULTS
According to IRS-1 and p-IRS-1 immumohistochemical staining, the expression of IRS-1 positive cells in hippocampus CA1 area in model mice was significantly higher than that of the normal control group (P<0. 01). Compared with the model group, the number of IRS-1 positive cells in hippocampus CA1 area decreased (P <0. 05 or P <0. 01) and the number of p-IRS-1 positive cells in hippocampus CA1 area increased in all of curcumin intervention groups. Western blot results were consistent with IRS-1 and p-IRS-1 protein expressions and immunohistochemistry results. RT-PCR test showed opposite IRS-1 mRNA expression results with immunohistochemistry and Western blot results.


CONCLUSIONS
Curcumin can recover increased IRS-1 and decreased p-IRS-1 in hippocampus of APP/PS1 double transgenic mice, increase IRS-1 mRNA expression, and improve the insulin-signaling transduction in APP/PS1 double transgenic mice. This suggests that curcumin can regulate the insulin-signaling transduction mechanism and show an anti-AD effect.
Grade III Laboratory of State Administration of Traditional Chinese Medicine, Key Laboratory of Pharmacology of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China. fenghuili1213@163.com
Hui-Li
HL
Feng
Rui-Sheng
RS
Li
Hong
H
Wang
Ying
Y
Ren
Hai-Yun
HY
Sun
Jin-Duo
JD
Yang
Peng-Wen
PW
Wang
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor; D055504:Insulin Receptor Substrate Proteins; D003474:Curcumin