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 AKT (serine-threonine kinase, AKT, also known as PKB) and p-AKT (phosphated serine-threonine kinase, p-AKT) in APP/PS1 double transgenic mice of the AD model.</p><p><b>METHOD</b>Three-month-old APP/PS1 double transgenic mice were randomly divided into the model group, the rosiglitazone (10 mg kg-1 . d-1) group, and high (400 mg . kg-1 d-1), medium (200 mg . kg-1 d-1) and low (100 mg kg-1 d-1) dosecurcumin groups. Non-transgenic mice of the same age and background were selected as the control group ( n = 12). After all of the six groups were intragastrically administered for consecutively three months, the protein expressions of AKT and p-AKT in hippocampus CA1 area were detected by immunohistochemistry and Western blot.</p><p><b>RESULT</b>The results of immunohistochemistry showed that the expression of AKT and p-AKT positive cells in hippocampus CA1 area significantly decreased in the model group (P <0. 05 and P < 0. 01). Compared with the model group, AKT and p-AKT positive cells of hippocampus CA1 area increased obviously in the rosiglitazone group and high and medium dose curcumin group (P <0.05 or P <0.01) ,especially the medium dose group (P <0.01). The results of Western blot were consistent with that of immunohistochemistry.</p><p><b>CONCLUSION</b>Curcumin can recover the decreased AKT and p-AKT cells in hippocampus CAl area of APP/PS1 double transgenic mice of the AD model, suggesting that curcumin may regulate AKT and its phosphorylation process, as well as PI3K/AKT insulin signal transduction pathway, and show the anti-AD effect.</p>
Subject(s)
Animals , Mice , Amyloid beta-Protein Precursor , Genetics , Metabolism , Blotting, Western , CA1 Region, Hippocampal , Curcumin , Pharmacology , Immunohistochemistry , Mice, Transgenic , Protein Serine-Threonine Kinases , Metabolism , Signal Transduction , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of curcumin on the expression of PI3K (phosphatidylinositol-3-kinase, PI3K) and p-P3 K (phosphated phosphatidylinositol-3-kinase, p-PI3K) in the hippocampus of Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice.</p><p><b>METHOD</b>A total of 60 three-month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group(10 mg . kg-1 . d-1) and curcumin large(400 mg . kg-1 . d-1), medium(200 mg- kg-1 . d-1) and small(100 mg . kg-1 . d-1) dose group. Twelve C57BL/6J mice in the same age and genetic background as APP/PS1 double transgenic mice were used as normal control group. All the 6 groups of mice were intragastrically administered for 3 months. After 3 months, the expression of PI3K and p-PI3K were detected by immunohistochemistry and Western blot.</p><p><b>RESULT</b>The expression of PI3K and p-PI3K positive cells in hippocampus CA1 region significantly decreased in model group compared with normal control group (P < 0. 05) , while compared with model group, PI3K and p-PI3K positive cells of all the curcumin intervention groups increased to varying degrees in hippocampus CA1 region,especially the middle dose group(P <0. 01). Besides,Western blot results of the curcumin high dose group were also increased obviously (P <0. 05).</p><p><b>CONCLUSION</b>Curcumin can recover the decreased PI3K and p-PI3K and improve the insulin-signaling transmission in the hippocampus of APP/PS1 double transgenic mice. The mechanism of curcumin maybe by regulating the insulin signal transduction to treat AD.</p>