Effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on the expression of DMT1 in the cerebral cortex of transgenic mice model of Alzheimer′s disease / 重庆医学

Objective To investigate the effects of Epimedium ,Astragalus ,Radix Puerariae on DMT1 expression in the cere‐bral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD .Methods A total of 60 specific‐pathogen‐free male APPswe/PS1ΔE9 double transgenic mice aged 6 months were equally and randomly assigned to model ,Epimedium ,Astragalus ,Radix puerari‐ae ,compound and DFO groups .An additional 10 6‐month‐old C57BL/6J mice served as negative control group .Using immunohisto‐chemistry and molecular biology methods to investigate the effects of a compound combining the effective components of Epimedi‐um ,Astragalus ,Radix puerariae on DMT1 expression in the cerebral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD . Results Immunohistochemical staining results revealed that DM T 1 positive cell did not show in negative control group .DM T1 ex‐pression was higher in model group compared with the negative control group .DMT1 expression was lower in the compound and deferoxamine groups than in the model group .No significant difference was detected in DM T 1 expression between deferoxamine and compound groups .RT‐PCR ,Western blot and immunohistochemical staining results showed no significant difference .Conclusion These compounds can downregulate DMT1 expression and inhibit iron overload in the cerebral cortex of mice with Alzheimer′s dis‐ease ,reduce iron overload induced impairment of the central nervous system .

Effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on behavioral and pathological changes in a transgenic mouse model of Alzheimer’s disease / 中国药理学通报

Aim To observe the effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on behavioral and pathological changes in a transgenic mouse model of Alzheimer’s disease.Methods Six-month-old APPswe /PS1 ΔE9 transgenic mice were ran-domly divided into 2 groups:model group and effective fraction group,1 0 mice each group.The mice in the effective fraction group were treated with the effective fraction of Astragalus,Radix Puerariae,Epimedium compound for 8 weeks.The C57BL/6J mice were used as negative control group.After 8 weeks,the learning and memory function were measured by Morris water maze,the pathological changes in brain tissue were ob-served by Modified Bielschowsky staining and Nissl 's staining.Results During place navigation trial,the escape latency in the APPswe /PS1 ΔE9 double transgenic model mice was longer than those of the mice of C57 (P 0.05 ). The Modified Bielschowsky staining shows that the neuron fibers of the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice were enlarged,swelling,and dense.There were senile plaques and nerve fiber tangles in the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice.The neuron fibers of mice in the effective fraction group were relieved;there was a small amount of senile plaque.The Nissl’s staining shows that the neurons of the cerebral cortex of APPswe /PS1 ΔE9 mice were edema, the number of cells were decreased.The mice in the effective fraction group were free of the disease.Con-clusion The double transgenic APPswe /PS1 ΔE9 mice of AD can simulate the specific pathogenesis of AD, which may be the efficient experimental animal model. The effective fraction of epimedium,astragalus and ra-dix puerariae may have a neuroprotective effect against AD via improving the learning and memory ability,and reduce the cerebral cortex nerve fiber tangles,senile plaques and neurons edema changes.

β-amyloid protein up-regulates the expression of the receptor for advanced glycation end products by increasing ROS production / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of β-amyloid protein (Aβ) in regulating the expression of the receptor for advanced glycation end products (RAGE).</p><p><b>METHODS</b>Aβ1-40 was injected into the bilateral hippocampus of rats, and 3 weeks later, the levels of reactive oxygen species (ROS) production were detected by flow cytometry. The expressions of RAGE, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (gp9l(phox) and p47(phox)), nuclear factor-κB (NF-κB), and inhibitor of κB (IκB) were measured by Western blotting.</p><p><b>RESULTS</b>Injection of Aβ1-40 caused a significant increase in the expressions of RAGE, gp9l(phox), p47(phox), phospho-p47(phox), phospho-IκBα, NF-κB and phospho-NF-κB in rat hippocampus but decreased the level of IκBα. Aβ1-40 injection also resulted in a significantly increased content of ROS in the hippocampus of the rats.</p><p><b>CONCLUSION</b>Aβ up-regulates the expression of RAGE in rat hippocampus via NADPH/ ROS/NF-κB signaling pathway.</p>

Alzheimer’s disease transgenic animal models:How to get more similar pathological characteristics? / 中国组织工程研究

BACKGROUND:Alzheimer’s disease causes and pathogenesis remain unclear, which greatly restrict the screening of drugs. And the main reason is lack of suitable animal models. The developing transgenic animal technology al ows studying the role of certain pathogenic gene in vivo, and has regarded the ideal animal models for Alzheimer’s disease. OBJECTIVE:To summarize the research advance of Alzheimer’s disease transgenic animal models. METHODS:Using“Alzheimer’s disease, transgenic mouse, animal model, dementia”in Chinese and English as the key words, the first author retrieved PubMed and CNKI databases published before July 2013. Final y, 41 articles were included in result analysis. RESULTS AND CONCLUSION:The etiology of Alzheimer’s disease is diverse, and genetic factor is one important factor. The existing transgenic animal models of Alzheimer’s disease include single genetical y modified models, double genetical y modified models and multiple transgenic models. Single transgenic animal models can make a kind of mutated exogenous gene integrate into the genomes of animals by using recombinant DNA technology. This kind of models can be applied to only study one specific pathological change of Alzheimer’s disease. Double transgenic animal models can make two kinds of mutated exogenous gene integrate into the genomes of animals and simultaneously transfect animals by using recombinant DNA technology. This kind of models is closer to the pathological changes of Alzheimer’s disease than single transgenic animal models, but stil cannot simulate Alzheimer’s disease. Multiple genetical y modified models are obtained with different transgenic mice hybridization or several genes transfection, which are most similar to clinical process and pathological features of Alzheimer’s disease. However, this kind of models may develop a decline in consanguinity. Each kind of animal model has their advantages and shortcomings, and a better transgenic animal model is urgently needed to completely simulate pathological characteristics of Alzheimer’s disease.

Study on effect and mechanism of salidroside on cognitive ability of Abeta1-40 -induced Alzheimer's disease model rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect and possible impact mechanism of salidroside on cognitive ability of Alzheimer's disease (AD) model rats induced by amyloid beta peptide (Abeta1-40).</p><p><b>METHOD</b>Abeta1-40 was injected into bilateral hippocampus to create the AD model. Afterwards, different doses of salidroside (25, 50, 75 mg x kg(-1)) were orally administered for 21 days. Rats' learning and memory abilities were detected by Morris water maze testing system. The levels of the superoxide dismutase (SOD), malondialdehyde (MDA), and the expression of nuclear factor-kappaB (NF-kappaB), inducible nitric oxide synthase (iNOS) and receptor for advanced glycation end products (RAGE) protein in hippocampus were also detected by different methods.</p><p><b>RESULT</b>The place navigation test showed longer escape latency, low frequency of platform quadrant crossing per unit time, damage in learning capacity, significant decrease in SOD acivity in hippocampus, notable increase in MDA content, NF-kappaB, iNOS and RAGE protein expressions in rats. Salidroside (50, 75 mg x kg(-1)) significantly alleviated the impairments of learning and memory ability. The activity of SOD increased in salidroside (50 droside group compared with that of the Alzheimer's disease group (P < 0.01).</p><p><b>CONCLUSION</b>Salidroside may treat Alzheimer's disease by inhibiting the oxidative stress.</p>

Effects of angiotensin II and its receptor blockers on migration and endothelin-1 expression of rat vascular adventitial fibroblast subpopulations / 药学学报

The study is to investigate the effect of angiotensin II (Ang II) and its receptor blockers on migration and endothelin-1 (ET-1) expression of rat vascular adventitial fibroblast subpopulations. Vascular adventitial fibroblasts were individually expanded by using cloning rings, and the effects of Ang II on the migration of adventitial fibroblast subpopulations were evaluated by Transwell. Fluorescence quantitative-PCR detected the expression of preproET-1 mRNA induced by Ang II, and its receptor antagonists losartan and PD-123319. The concentration of ET-1 was determined by ELISA. It showed that spindle shaped and epithelioid shaped cells were isolated by using cloning rings, named as spindle cells and round cells. RT-PCR showed that fibroblast subpopulations did not have leukocytes, endothelial cells and smooth muscle cells, namely pure cell lines. Compared with respective control cells, two subpopulations had transferring ability. Ang II significantly improved round cells migration in a concentration-dependent manner, and had no obvious influence on spindle cells migration. Ang II (1 x 10(-8) - 1 x 10(-6) mol x L(-1)) significantly increased the expression of preproET-1 mRNA in round cells (P < 0.01), and had no significant effect on the expression of preproET-1 mRNA in spindle cells. Losartan blocked the expression of preproET-1 mRNA induced by Ang II in round cells, and had no significant effect on the expression of preproET-1 mRNA in spindle cells. The effects of Ang II and ET-1 receptor inhibitors on the release of ET-1 were similar to the expression of preproET-1 mRNA. The results indicate that there are two cell subpopulations: round cells and spindle cells in rat vascular adventitial fibroblasts. Ang II significantly improved cells migration, and increased the expression of ET-1 in round cell subpopulation. It suggested that there may be different migratory mechanisms in two cell subpopulations, and the two subpopulations may play a different role in vascular remodeling and reparative process.

Effects of carbamazepine on the morphology of astrocytes and GFAP expression in hippocampus of rats / 基础医学与临床

Obiective To observe the effects of carbamazepine on morphology and glial fibrillary acidic protein(GFAP)expression of astrocytes in hippocampus of Sprague-Dawley rats.Methods Astrocytic expression was observed with GFAP immunohistochemical staining.Results Compared to control group,GFAP immunoreactivity and the number of GFAP-positive astrocytes were significantly increased after 3 months of carbamazepine administration.Conclusion The changes of astrocytic expression induced by carbamazepine are time-dependent.

Mechanism of mitochondrial dysfunction and ultrastructural changes induced by rotenone in PC12 cells / 第三军医大学学报

Objective To observe the effects of different doses of rotenone on reactive oxygen species, mitochondrial transemembrane potential as well as mitochondrial ultrastructure in order to investigate the possible mechanism of mitochondrial dysfunction in cultured pheochromaffinoma cells. Methods ROS production induced by rotenone in cells were measured using flow cytometry. Mitochondrial transmembrane potential was detected by laser scanning confocal microscope and mitochondrial ultrastructures were observed under transmission electron microscope. Results Treatment with 0.1, 1.0, 2.0 and 3.0 ?mol/L concentrations of rotenone could increase the generation of ROS in PC12 cells as 1.55?0.17, 2.16?0.10, 1.77?0.20 and 1.40?0.12, and disrupt the mitochondrial transmembrane potential about 93.86?10.12, 119.43?7.09, 102.71?9.36 and 83.14?10.70. There were significant differences as compared with the control group (P

Effect of human hypoxia inducible factor-1? gene transfection on apoptosis of A?25-35 induced hippocampal neurons of primary culture / 第三军医大学学报

Objective To construct the eukaryotic expression vector for human hypoxia inducible factor-1? gene (pSNAV-HIF-1?), and to investigate the apoptosis and intracellular calcium concentration of the transfected A?25-35 induced hippocampal neurons of primary culture. Methods Human hypoxia inducible factor-1? gene from pBSKhHIF1?T7 was inserted into pSNAV2.0 by the method of gene recombination, then the constructed vector was transfected into hippocampal neurons of primary culture and followed by A?25-35 for treatment. Empty pSNAV2.0 vector was treated the same way as pSNAV-HIF-1? as a control. The expression level of HIF-1? protein was assayed by Western blotting. Apoptosis was detected by flow cytometry. Intracellular calcium concentration was determined by laser scanning confocal microscopy with Fluo-3/AM as the fluorescent dye. Results It was shown that pSNAV-HIF-1? was successfully constructed by restriction enzyme digestion, PCR and DNA sequencing. The expression level of HIF-1? protein was significantly increased in transfected hippocampal neurons of primary culture (P

Calcium mechanism of endoplasmic reticulum stress and the change of ultrastructures induced by rotenone in PC12 cells / 中华神经科杂志

Objective To investigate the calcium mechanism of endoplasmic reticulum stress and the changes of ultrastructure induced by rotenone. Methods Rotenone induced reactive oxygen species(ROS) production in PC12 cells were measured by using flow cytometry(FCM). Relative changes of intracellular calcium concentration were monitored by use of laser scanning confocal microscope. The ultrastructures were observed under transmitting electronic microscope. Results Treatment with different concentrations of rotenone ( 0.1 ?mol/L,1.0 ?mol/L,2.0 ?mol/L and 3.0 ?mol/L )increased the ROS generation in PC12 cells, and fluorescence intensity (FI) value was shown as 1.55?0.17, 2.16?0.10, 1.77?0.20 and 1.41?0.12, respectively. The same concentration of rotenone resulted in the elevation of intracellular calcium,the relative changes of fluorescence intensity about 0.6029?0.0685,1.0902?0.1127,0.7479?0.0820 and 0.5614?0.0870. There were significant differences as compared with those in control group (P

High brain iron in etiology of Alzheimer's disease and therapeutic approaches / 中国药理学通报

Excessive iron accumulation in the brain occurs in Alzheimer' s disease (AD) with oxidative stress,amyloid deposition,tau phosphorylation,and neuronal cell cycle regulatory failure,leading to apoptosis.Therefore,there is a direct link between iron metabolism and AD pathogenesis. The present review elaborates on high brain iron in etiology of AD and the development of iron-chelating therapy for AD,aiming at preventing or slowing down disease evolution.

The RAGE-A? interaction and its effects on pathogenesis of Alzheimers disease / 中国药理学通报

Receptor for advanced glycation end products(RAGE) is a member of the immunoglobulin superfamily.In central nervous system,RAGE is mainly expressed by neurons,microglia,and cerebral endothelial cells.In Alzheimers disease(AD) brain,levels of RAGE are significantly increased from the positive feedback mechanisms driven by excess amounts of ?-amyloid protein(A?).The interaction of RAGE with A? in neurons,microglia,and cerebral endothelial cells induces the perturbation of neuronal functions,amplification of microglia inflammatory responses,and vascular dysfunction.Further understanding the molecular mechanisms associating RAGE-A? interaction provides us the opportunity to develop the therapeutic approaches for the devastating disease.