Effects of on behavior and blood-brain barrier in Alzheimer's disease mice / 浙江大学学报·医学版

To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.

Impact of maternal gestation combined exposure to lead and mental stress on offspring's fear-conditioning memory / 上海交通大学学报（医学版）

Objective: To explore whether prenatal stress can enhance the accumulation of blood/bone lead in the offspring on the basis of prenatal lead exposure, and to compare the effects of prenatal single exposures to stress/lead and prenatal combined exposure to lead and stress on fear-conditioning memory in the offspring. Methods: Pregnant rats were randomly divided into control group, stress exposure group, lead exposure group and combined lead-stress exposure group. After delivery, each group contained twelve pups (male:female=1:1). The extinction process of fear-conditioning memory was evaluated by the fear-conditioning test in the offspring at 3 weeks old. The offspring were then sacrificed at 4 weeks old. Blood and tibia samples were collected, blood lead was measured by using the atomic absorption spectrometer, and tibia lead was measured by using the inductively coupled plasma-mass spectrometry. The levels of blood lead, bone lead and fear memory were compared by analysis of variance, and the relationship between blood lead, bone lead and fear memory were analyzed by Logistic regression model. Results: The levels of blood and bone lead in the lead exposure group (P blood lead=0.013, P bone lead=0.000) and combined exposure group (P blood lead=0.000, P bone lead=0.000) were significantly higher than those in the control group; the level of blood lead in the stress group was higher but not significantly different from that in the control group (P blood lead=0.056) and the level of bone lead in the stress group was significantly higher than that in the control group (P bone lead=0.004); the levels of blood and bone lead in combined exposure group were higher than those in the lead exposure group, but the differences didn’t reach statistical significance (P blood lead=0.682, P bone lead=0.124). Compared with young rats in the lowest blood lead/bone lead groups, young rats in the groups of higher blood/bone lead levels had higher odds ratios of high fear reaction during the second (P=0.008/P=0.016) and the third (P=0.019/P=0.005) time periods. The ratios of freezing time in the first [(83.73±25.47)%] and the second [(92.97±15.75)%] periods of the fear-conditioning test in the combined exposure group were significantly higher than those in the control group [the first period, (65.35±28.80)%, P1=0.048; the second period, (68.78±27.22)%, P2=0.021]. Conclusion: Compared with the single exposure to lead during pregnancy, maternal gestation combined exposure to lead and stress may induce more increases in the blood and bone lead levels in the offspring. Lead exposure during pregnancy may inhibit the process of the extinction of fear memory in the offspring, and this effect may be aggravated by prenatal concurrent exposure to stress.

A novel fear conditioning memory model formation and erasing by foot-shock in tree shrew / 安徽医科大学学报

Objective To investigate the way of fear conditioning memory model evoked and erased by foot-shock in tree shrew. Methods First, detect the tree shrew activities regularly in light/dark box. Second, test a suitable voltage degree of foot shock on tree shrew. Third, investigate the memory formation and erasing of fear conditioning on tree shrew of trial group. Results The duration of tree shrew (n=4) stay in the dark-box was significantly lon-ger than that of in the light box (P<0. 01) in normal condition. In the same environment of two light boxes, given different voltage degrees, the durations of tree shrew (n=6) stay in the stimulating chamber gradually reduced and the durations of tree shrew stay had significant difference between stimulatus chamber and no stimulatus chamber when the stimulus voltage up to 12 V ( P<0. 05 ) , 16 V ( P<0. 01 ) and 20 V ( P<0. 01 ) . The animal of trial group ( n=4 ) could build up the fear conditioning memory of the dark box with the stimulus of 16 V foot-shock in the dark box ( P<0. 001 ) . After formation of the fear conditioning memory, the same stimulus in light box ap-peared for 4 days. The durations of tree shrew stay in trial group (n=4) decreased in light box, and there was no significant difference between the trial group and the control group. Conclusion Tree shrew prefers to stay in the dark box. The suitable voltage for foot-shock on tree shrew is 16 V. The fear conditioning memory can be evoked and erased by foot-shock.