ABSTRACT
OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on learning-memory ability and the expression of senile plaques (SP), amyloid precursor protein (APP), β-secretase 1(BACE 1) and insulin degrading enzyme (IDE) in the hippocampus in APP/presenilin 1 (PS 1) double transgenic Alzheimer's disease (AD) mice, so as to reveal its mechanisms underlying improvement of AD. METHODS: A total of 18 male APP/PS 1 double transgenic AD mice were randomly divided into model, EA-2-week and EA-3-week groups (n=6 in each). The control group was consisted of 6 male wild mice. EA (2 Hz, 2 mA) was applied to "Baihui" (GV 20) and bilateral "Shenshu" (BL 23) for 15 min, once a day, with 7 days being a therapeutic course, 2 or 3 courses altogether and with an one day's interval between every two courses. The spatial learning-memory ability was assessed using Morris water maze test during 5 days' training. The immunoactivity of SP in the hippocampus tissue was detected by immunohistochemistry, and the expression levels of APP, BACE 1 and IDE in the hippocampus were analyzed by Western blot. RESULTS: Following modeling, the escape latency and path length of hidden platform tests were significantly increased (P<0.01, P<0.05), and the platform crossing time of spatial probing test significantly decreased (P<0.01) in the model group compared with the control group. After EA intervention, the escape latency on the 5th day of training, and the path length on the 4th and 5th day of training in both EA-2-week and EA-3-week groups were significantly shorter relevant to the model group (P<0.01), and those of the EA-3-week group were considerably shorter than those of the EA-2-week group in the escape latency and path length (P<0.05, P<0.01). The platform crossing times of spatial probing test were significanthy increased in both EA-2-week and EA-3-week groups in comparison with the model group (P<0.01), and that of the EA-3-week group was considerably increased compared with the EA-2-week group (P<0.05). Immunohistochemical staining showed that the number of SP in the hippocampus was markedly increased in the model group compared with the control group (P<0.01), and was markedly reduced in both EA-2-week and EA-3-week groups (P<0.01), and that of the EA-3-week group was significantly decreased compared with the EA-2-week group (P<0.01). The expression levels of hippocampal APP and BACE 1 proteins were significantly higher in the model group than in the control group (P<0.01), and that of hippocampal IDE was markedly lower in the model group than in the control group (P<0.01). After EA, the increased expression levels of APP and BACE 1 proteins and the decreased expression level of IDE in the EA-2-week and EA-3-week groups were significantly inhibited (P<0.01). The effects of EA-3-week were significantly stronger than those of EA-2-week in down-regulating the expression of APP and BACE 1 proteins and up-regulating the expression of IDE (P<0.01, P<0.05). CONCLUSION: EA stimulation of GV 20 and BL 23 can improve the learning-memory ability in APP/PS 1 double transgenic AD mice, which may be related to its effects in down-regulating the expression of SP, APP and BACE 1 proteins and up-regulating the expression of IDE protein in the hippocampus.
ABSTRACT
Presenilin (PS) is a transmembrane protein identified in familial early-onset Alzheimer disease, and it is mainly expressed in cell membranes and organelle membranes. As an important catalytic core of the γ-secretase multimeric enzyme complex, PS has been implicated in regulating various proteins. Recent researches have shown that mutations in PS are identified in the familial dilated cardiomyopathy, and the PS gene plays an important role in cardiac formation and regulation of calcium homeostasis in myocardial cells. In this review, we summarized the function of PS in heart and the mechanisms underlying the effects of PS on calcium homeostasis, such as amyloid β protein (Aβ), 1,4,5-inositol trisphosphate receptors, ryanodine receptors and PS as endoplasmic reticulum (ER) Ca2+ leak channels, hoping to provide a theoretical basis for the therapy of dilated cardiomyopathy.
ABSTRACT
Objective·To investigate the effects of insulin-like growth factor 1 on prion encoding gene (PRNP) expression and amyloid precursor protein (APP) metabolism of PC12 cells. Methods·After PC12 cells were treated with 20, 40, 80 ng/mL IGF-1 for 24 h, real-time PCR was used to detect the mRNA expression levels of PRNP, and Western blotting was used to detect the protein levels of AKT, phosphorylation of AKT (pAKT), ERK and phosphorylation of AKT (pERK). The level of β-amyloid 42 (Aβ42) in supernatant fluid was detected by ELISA. Results·Compared with the blank control group, the expression of PRNP mRNA in Alzheimer's disease (AD) model group was increased significantly (P0.05). Compared with the blank control group, the level of Aβ42 in supernatant fluid of model group was decreased significantly with the increasing of IGF-1 concentration. The expression level of Aβ42 was decreased significantly in 40 and 80 ng/ml IGF-1 treatment group (P<0.05). The expression of AKT/pAKT, ERK/pERK in AD model group was significantly increased along with the increasing of IGF-1 concentration (P<0.05). Conclusion·IGF-1 could regulate the expression of PRNP gene and effect the metabolism of APP, which may be associated with PI3K/AKT, MAPK/ERK1/2 signaling pathway.