ABSTRACT
<p><b>OBJECTIVE</b>To observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin.</p><p><b>METHOD</b>APPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions.</p><p><b>RESULT</b>Both of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P < 0.01). IHC showed a lower result in the Rosiglitazone group than the model group (P < 0.05), while Western blot showed a much lower result (P < 0.01). The number of Aβ40, Aβ42 and ADDLs positive cells and the protein expressions decreased in the curcumin high group, the medium group showed a significant decrease (P < 0.01), and the low dose group also showed reductions in the protein expressions of Aβ40 and Aβ42.</p><p><b>CONCLUSION</b>The six-month intervention with curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aβ cascade reaction by down-regulating expressions of Aβ40, Aβ42 and ADDLs and show the neuroprotective effect needs further studies.</p>
Subject(s)
Animals , Humans , Mice , Alzheimer Disease , Drug Therapy , Genetics , Metabolism , Amyloid beta-Peptides , Genetics , Metabolism , Brain , Metabolism , Curcumin , Disease Models, Animal , Hippocampus , Metabolism , Mice, Inbred C57BL , Mice, Transgenic , Neuroprotective Agents , Plant ExtractsABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>