Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity

Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer＇s disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B （NR2B） expression. An APP695V7171 transgenic mouse model of Alzheimer＇s disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer＇s disease.

Effects of Adipose-derived Mesenchymal Stem Cell Exosomes on Corneal Stromal Fibroblast Viability and Extracellular Matrix Synthesis

Background： Corneal stromal cells （CSCs） are components of the corneal endothelial microenvironment that can be induced to form a functional tissue-engineered corneal endothelium. Adipose-derived mesenchymal stem cells （ADSCs） have been reported as an important component of regenerative medicine and cell therapy for corneal stromal damage. We have demonstrated that the treatment with ADSCs leads to phenotypic changes in CSCs in vitro. However, the underlying mechanisms of such ADSC-induced changes in CSCs remain unclear. Methods： ADSCs and CSCs were isolated from New Zealand white rabbits and cultured in vitro. An Exosome Isolation Kit, Western blotting, and nanoparticle tracking analysis （NTA） were used to isolate and confirm the exosomes from ADSC culture medium. Meanwhile, the optimal exosome concentration and treatment time were selected. Cell Counting Kit-8 and annexin V-fluorescein isothiocyanate/ propidium iodide assays were used to assess the effect of ADSC-derived exosomes on the proliferation and apoptosis of CSCs. To evaluate the effects ofADSC-derived exosomes on CSC invasion activity, Western blotting was used to detect the expression of matrix metalloproteinases （MMPs） and collagens. Results： ADSCs and CSCs were successfully isolated from New Zealand rabbits. The optimal concentration and treatment time of exosomes for the following study were 100 μg/ml and 96 h, respectively. NTA revealed that the ADSC-derived exosomes appeared as nanoparticles （40-200 nm）, and Western blotting confirmed positive expression of CD9, CDSI, flotillin-1, and HSP70 versus ADSC cytoplasmic proteins （all P〈 0.01 ）. ADSC-derived exosomes （50μg/ml and 100μg/ml） significantly promoted proliferation and inhibited apoptosis （mainly early apoptosis） of CSCs versus non-exosome-treated CSCs （all P 〈 0.05）. Interestingly, MMPs were downregulated and extracellular matrix （ECM）-related proteins including collagens and fibronectin were upregulated in the exosome-treated CSCs versus non-exosome-treated CSCs （MMPI： t = 80.103, P 〈 0.01; MMP2： t = 114.778, P 〈 0.01; MMP3： t = 56.208, P 〈 0.01; and MMP9： t = 60.617, P〈 0.01; collagen I： t = -82.742, P〈 0.01; collagen II： t = -72.818, P〈 0.01; collagen III： t = -104.452, P〈 0.01; collagen IV： t = - 133.426, P 〈 0.01, and collagen V： t - -294.019, P 〈 0.01 ; and fibronectin： t = -92.491, P 〈 0.01, respectively）. Conclusion： The findings indicate that ADSCs might play an important role in CSC viability regulation and ECM remodeling, partially through the secretion of exosomes.

Comorbidity Burden of Dementia:A Hospital-Based Retrospective Study from 2003 to 2012 in Seven Cities in China

Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer＇s disease（AD）, vascular dementia（Va D）, or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January2003 to December 2012. The Charlson Comorbidity Index（CCI） was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had Va D, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients,3.4 ± 1.8 for those with Va D, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, andthe length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.

Ginsenoside Rd improves behavioral impairment of rats with acute plateau status by modulating synaptic plasticity

Objective:To investigate the protective effect of ginsenoside Rd on the improvement of the behavior and synaptic plasticity in rats with acute plateau status.Methods:A total of 60 Wistar rats were randomly divided into the control group,the model group,and the intervention group,with 20 rats in each group.The model was established in low-pressure oxygen chamber simulating the plateau,and the intervention group was administered with ginsenoside.Electron microscope was used to observe synaptic ultrastructure of hippocampal CA1 area,and analyze the structural parameters on the Gray I synaptic interface.Morris water maze and Y electric maze experiment were used for behavioral detection.Results:Compared with the control group,the number of electrical stimulation required for rat to avoid was increased in the model group,the latency in the Morris water maze was prolonged,the swimming distance was increased,and the frequency of crossing the platform was decreased.Under the electron microscope,the synaptic cleft was increased,the length of the synaptic active area was shorter,the postsynaptic density(PSD)was thinner,the flat synapse was increased,and the concave and perforated types were significantly reduced.Compared with the model group,the number of electrical stimulation required for rat to avoid was decreased in the intervention group,the latency in the Morris water maze was shortened,the swimming distance was decreased,and the frequency of crossing the platform was increased.Under the electron microscope,the synaptic cleft was decreased,PSD was thicker,the flat synapse was decreased,and the concave and perforated types were increased.Conclusion:Low pressure and low oxygen environment of plateau damages the plasticity changes of the synaptic structure and function.And to a certain extent,ginsenoside Rd reverses Gray I synaptic interface structure parameters,so as to improve the behavior performance of model rats at high altitude condition.

PERK Signaling of Unfolded Protein Response Actived in Acute Hypobaric Hypoxia and Effect of Ginsenoside Rb1

Objective To observe pancreatic ER kinase （PERK） signaling of unfolded protein response （UPR）. Methods The rats were divided into control, model, and ginsenoside Rb; （Rbl） groups, and put into hypoxia chamber to establish the acute plateau stress model. The water solutions of Rbl were given to rats in Rb; group for 7 d. After that, The behavior of rats was observed by Y-maze and passive avoidance test and the rats were sacrificed in a batch for detection by Western blotting. Results Hypobaric hypoxia mediated UPR pathway accompanied the activation of protective pathways such as PERK-elF2a-ATF4 and Grp78/Bip pathways. On the other hand, RbT, the extract from herbal medicine ginseng, increased on the expression of PERK, eIF2a, ATF4, and Grp78/Bip in rats. Conclusion The results indicate that PERK-elF2a-ATF4-GRP78 pathway is a potential target for therapeutic applications in high altitude diseases and Rb] can attenuate the injury to memory function caused by hypobaric hypoxia neurotoxicity.