Impaired cognitive map in transgenic animals relevant to Alzheimer's disease: from neurons to network / 生理学报

Alzheimer's disease (AD) is a typical cognitive disorder with an increasing incidence in recent years. AD is also one of the main causes of disability and death of the elderly in current aging society. One of the most common symptoms of AD is spatial memory impairment, which occurs in more than 60% of patients. This memory loss is closely related to the impairment of cognitive maps in the brain. The entorhinal grid cells and the hippocampal place cells are important cellular basis for spatial memory and navigation functions in the brain. Understanding the abnormal firing pattern of these neurons and their impaired coordination to neural oscillations in transgenic rodents is crucial for identifying the therapeutic targets for AD. In this article, we review recent studies on neural activity based on transgenic rodent models of AD, with a focus on the changes in the firing characteristics of neurons and the abnormal electroencephalogram (EEG) rhythm in the entorhinal cortex and hippocampus. We also discuss potential cell-network mechanism of spatial memory disorders caused by AD, so as to provide a scientific basis for the diagnosis and treatment of AD in the future.

The role and mechanism of SIRT1 gene in depression / 生理学报

As a kind of mental illness, depression produces great difficulties in clinical diagnosis and treatment, and has a high disability rate. It is urgent to clarify the mechanism of depression to find potential therapeutic targets and effective clinical treatment methods. As a deacetylase, silent mating type information regulator 2 homolog 1 (SIRT1) is involved in many biological processes such as cell aging, cancer, and cardiovascular disease. In recent years, more and more studies have found that SIRT1 gene plays an important role in the pathogenesis of depression, but the mechanism is still unclear. Therefore, this review mainly summarizes the relevant research progress on the role and mechanism of SIRT1 gene in the hippocampus, prefrontal cortex, amygdala, hypothalamic suprachiasmatic nucleus, and nucleus accumbens in depression, in order to provide new ideas for exploring the mechanism and prevention of depression.

Preparation of citronellol self-emulsifying delivery system and evaluation of its in vitro antitumor activity / 中草药

Objective: To investigate the effect of citronellol (citronellol, CT) on the proliferation of HEp-2 and MCF-7 cells, and prepare CT self-emulsifying drug delivery system (CT-SMs). Its antitumor activity and cell uptake ability of HEp-2 cells in vitro was evaluated. Methods: The effect of CT on the cell proliferation of HEp-2 and MCF-7 were investigated by MTT assay. The pseudo- ternary phase diagram method was used to optimize the formulation of CT-SMs, and the appearance morphology, mean particle size, and Zeta potential were characterized. The effect of CT-SMs on the proliferation of HEp-2 cells was detected by MTT assay and cellular uptake was determined by fluorescence inversion microscopy and flow cytometry. Results: After a certain concentration of CT treatment, MCF-7 cells proliferation was not affected, and the difference was not statistically significant (P > 0.05 compared with the control group), while the proliferative capacity of HEp-2 cells was significantly inhibited (P < 0.05 compared with the control group) in a dose-time dependent manner. The best prescription for CT-SMs was as following: Km (emulsifier:co-emulsifier) was Kolliphor® HS 15:absolute ethanol = 7:3, CT:Km = 3:7, the mean particle size was (354.0 ± 9.5) nm, the appearance was round and spherical with uniform distribution, and the Zeta potential was (-13.4 ± 0.3) mV. The results of cellular uptake experiments showed that the intake of CT-SMs (545.70 ± 11.56) was higher than that of CT (230.00 ± 17.76) in HEp-2 cells treating the same concentration of CT-SMs and CT. Conclusion: CT-SMs could significantly inhibit the proliferation of HEp-2 cells. In this study, CT-SMs were successfully prepared by dropping water method and the quality of CT-SMs was stable and controllable.

Optimization of formulation of paeonol lipid microspheres by central composite design-response surface method and its drug release mechanism in vitro / 中草药

Objective: To optimize the formulation of paeonol lipid microspheres (Pae-LM) through central composite design- response surface method and determine its in vitro release characteristics. Methods: Using the mean particle size and centrifugal stability constant (Ke) as evaluation indexes, the oil phase type and the ratio of composite oil, the amount of phospholipid and stearic acid, the type of emulsifier, the type and amount of stabilizer, the quality of PC and CH, the high-speed shear temperature and time, the homogenization pressure and time was screened in prescription process. Effects of dosage of paeonol and high pressure homogenizing pressure on the properties of Pae-LM preparation were investigated by central composite design-response surface method. The binomial model and multivariate linear regression model were used to establish the mathematical relationship between the indexes and the factors. According to the best mathematical model of evaluation index, the response surface was depicted and the best prescription was analyzed by the response surface method. According to the optimized formulation Pae-LM, the in vitro drug release characteristics were investigated. Results: The best prescription of Pae-LM was basically round, with mean particle size of (149.32 ± 0.57) nm, Zeta potential of (-36.01 ± 3.09) mV, encapsulation rate of (98.24 ± 0.32)% and drug-loading rate of (11.94 ± 0.04)%. There was a credible quantitative relationship between Ke and the two factors, and the binomialmodel was more reliable than the multivariate linear model. The cumulative release of paeonol drug substance at 12, 24 and 36 h were 71.84%, 85.21% and 95.07%, while the cumulative release of Pae-LM was only 57.21%, 59.66%, and 63.91% at 12, 24 and 36 h, respectively. The drug release was in accordance with the Ritger-peppas model. Conclusion: Central composite design-response surface method can be applied to optimize prescription of lipid emulsion microspheres. The optimized particle size of Pae-LM was suitable with a higher encapsulation rate, which can provide a reference for the development of paeonol cardiovascular delivery system.

Progress in the encoding characteristics and mechanisms of hippocampal neural assemble sequences in spatial memory / 生理学报

The formation, consolidation and retrieval of spatial memory depend on sequential firing patterns of place cells assembling in the hippocampus. Theta sequences of place cells during behavior play a role in acquisition of spatial memory, trajectory prediction and decision making. In awake rest and slow wave sleep, place cell sequences occur during the sharp wave-ripples (SWRs), called "replay", which is crucial for memory consolidation and retrieval. In this review, we summarize the functional significances of theta sequences and SWRs replay sequences and the mechanism of these sequences. We also discuss the relationship between theta and replay sequences with the formation of spatial memory. We propose the research direction in this field in future and aim to provide new ideas for related researches.

Preparation of Oxymatrine Phospholipid Complex Solid Lipid Nanoparticles Lyophilized Powder and Evaluation of Its Quality / 中国实验方剂学杂志

Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles(OMT-PC-SLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion;single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index;the morphology of this preparation was observed by transmission electron microscope(TEM).The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined. Result: Optimal formulation process was as following:taking soybean phospholipid and polyethylene glycol 15-hydroxystearate(Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier(Km)=3:2,oil phase:(emulsifier+co-emulsifier)=1:9,oxymatrine phospholipid complex-stearic acid-soybean phospholipid-Kolliphor HS 15-ethanol(30:100:180:360:360);taking 50 mL of 4%mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min-1 and solidifying for 1 h,precooled at -20℃ for 24 h,took out and dried for 24 h.OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of (38.09±1.24)%,average particle size of 785.5 nm,polydispersity coefficient(PDI) of 0.456 and the Zeta potential of -24.82 mV.The cumulative release rates of OMT-PC-SLN lyophilized powder were 72.63%at 2 h and 98.42%at 12 h;the cumulative release rate of oxymatrine(crude drug) was 98.60%at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability;compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.

Progress in the application of neural oscillations cross-frequency coupling in cognitive function research / 生理学报

Neural oscillations cross-frequency coupling (CFC) refers to the effect of the cross modulation between the electrophysiological oscillation rhythm in different ensembles of neurons. The CFC can reflect the mechanism of information transfer and exchange of local field potentials, electroencephalograph (EEG) and other neural electrophysiological activities at different spatial and temporal scales and plays an important role in the study of cognitive function. This paper introduces the basic phenomenon and classifications of neural oscillation CFC briefly, and reviews the typical applications in the study of the animal cognition model and human cognitive function in recent years, respectively. The main problems are also summarized and the future research is prospected in order to provide new ideas to promote the study and application of the CFC.

Progress in mechanisms underlying melamine toxicity in central nervous system / 生理学报

In recent years there have been more widely and deeply studies in investigating melamine toxicity. Generally, it is believed that the main target of melamine is the urinary system. However, previous studies revealed that it also had additional biological actions. Obviously, the toxicity mechanisms of melamine have not been fully clarified. It is well known that fetus and infant periods play the most fundamental role in the brain development. And melamine can pass through the placental and blood-brain barrier, and then exerts toxic effects on the central nervous system. This article reviewed the reports about the topic in recent years, for better understanding the dangers of melamine to infants and providing experimental data for further study.

Effect of a Chinese herbal prescription on collagen I in rat's femur under simulated weightlessness / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the effect of a Chinese herbal prescription on collagen I in rat's femur under simulated weightlessness.</p><p><b>METHODS</b>Thirty Wistar rats were randomly divided into 3 groups: blank control group (10 rats), tail suspension group (TS, 10 rats), TS with Chinese medicine group (10 rats). Rats in TS with Chinese medicine group took a Chinese herbal prescription (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid)by oral administration. After 1 week adaption and 3 weeks tail suspending, rat's left femur was colleced, and collagen I in femur neck was detected by immunohistochemical method.</p><p><b>RESULTS</b>Counts and integral optical density (IOD) of collagen I coloration decreased significantly in TS group (P < 0.001), but no significant change in TS with Chinese medicine group (P > 0.05), as compared with control group.</p><p><b>CONCLUSION</b>Generation of collagen I become weaken under simulated weightlessness, while the Chinese herbal prescription is effective to prevent the change, thus biochemistry environment of bone calcium deposition may be improved by this Chinese herbal prescription under simulated weightlessness.</p>

Comparison of effects of Wujia Bugu decoction) and alendronate sodium on protection the bone loss of hindlimb unloaded rats / 中国骨伤

<p><b>OBJECTIVE</b>To compare the effects of Wujia Bugu decoction and Alendronate sodium on protecting bone and muscle loss of hindlimb unloaded rats lasting three weeks.</p><p><b>METHODS</b>March to May, 2009, 40 male Wistar rats with age of 6-week, were randomized divided to four groups (10 rats in each group): hindlimb unloaded group treated with Chinese medicine (HUC), hindlimb unloaded group treated with alendronate sodium (HUA), control group (CON), as well as hindlimb unloaded group (HU). During the experiment, rats of HUC was given Wujia Bugu decoction (including the Ciwujia, Shudihuang, Huainiuxi, Muli, etc. with the concentration of 0.704 g/ml) 10 ml/kg weight once a day, HUA was given quantitative alendronate sodium slice dissolve suspension (0.9 mg/ml) once a week. CON and HU were given double-distilled water. The experiment lasted 4 weeks,from the second to the forth week, rats in HU, HUC, HUA were hindlimb unloaded. All rats were sacrificed at the fourth weekend, the content of Ca, P and the activation of ALP in serum, Bone mineral density (BMD) of humerus and femurs, Biomechanical property of tibia and humerus, as well as the weight index of biceps and sural muscles were measured.</p><p><b>RESULTS</b>Compared with CON, serum Ca of HU was significantly increased (P < 0.05), BMD, mechanical properties, muscle index of hindlimb were significantly reduce (P < 0.01), the serum Ca of HUA significantly increased (P < 0.05). Serum ALP of HUC was significantly higher than other three groups (P < 0.01). Compared with HU, femoral BMD of HUC and HUA significantly increased, tibial maximum load, maximum deflection and elastic load had increased tendency; calf muscle atrophy of HUC and HUA was alleviate 50% and 12.5% respectively (P > 0.05), humeral BMD had no significant difference, while the maximum deflection (P < 0.01) and elastic deflection (P < 0.05) in humerus of HUA were significantly lower.</p><p><b>CONCLUSION</b>Herbal prescription and alendronate sodium can effectively protect the bone and muscle loss of hindlimb unloaded rats, improve its mechanical structure. Herbal prescription has advantages of relieving mechanical properties change. The effects of Wujia Bugu decoction and alendronate sodium are similar in treating space weightlessness bone loss.</p>