Protective effect of amyloid-beta 42 protein and its subunit vaccines immunization on spatial learning and memory of APPSWE transgenic mice / 中国组织工程研究

ABSTRACT

BACKGROUND: It has been demonstrated that amyloid-beta 42 protein (Aβ42) immunization in transgenic mouse models of Alzheimer disease(AD)can induce specific Aβ42 antibody, clear Aβ from the brain, and thereby improve spatial learning and memory. It has been a promising treatment strategy for AD.OBJECTIVE: To explore the effect of Aβ42 and its subunit vaccines immunization on spatial learning and memory of APPSWE transgenic mice.DESIGN: A randomized controlled experiment with mice as subjects.SETTING: The brain research laboratory of the anatomy department in a the medical college of a univeristy.MATERIALS The experiment was conducted in the Experimental Animal Center and the Anatomy Department of Sun Yat-sen University from April 2003 to February 2004. Thirty-two APPSWE transgenic mice of 5 months old were bought from Taconic Company, USA. The second generation of mice were successfully reproduced in the Anatomy Department. These mice were randomly assigned into four groups control group, Aβ42 group, Aβ1-15group, and Aβ36-42 group. Each group contained 8 in each group.INTERVENTIONS: Aβ42 and its subunits combined with MF59 adjuvant were subcutaneously injected for fundamental immunity and then applied in nasal mucosa for intensified immunization. The immunization period was 8 months. Y-maze was used for behavior test before immunization and Morris water maze was used after immunization.MAIN OUTCOME MEASURES: Spatial learning and memory, mean escape latency, times of passing through the platform point, swimming distance percentage of the first quadrant, and swimming distance percentage of the 20% marginal area.RESULTS: The correct reaction times in Y-maze behavior test were 7.50 ±0. 81, 7.06 ±0.71, 7.19 ±0.91, and 7.50 ±0.86 respectively in the control, Aβ42, Aβ1-15, Aβ36-42 groups and there was no significant difference ( P ＞ 0. 05) . After immunization, the mean escape latencies in 8 units of localized navigation test were(67.3 ±2. 8) s, (23.6 ± 1.6) s, (26.4 ±2.0) s,and (36.5 ± 2.2) s. The results in three experiment groups were different from that in control group and there was no difference between the three experiment groups ( P ＞ 0. 05 ) . The mean times of passing through the platform point in the 4 groups were 0.71 ±0.29, 8.14 ± 1.37, 7.28 ± 1.34,and 3.29 ± 0. 67. Swimming distance percentage of the first quadrant in the4 groups were(24.3 ±2.9)%, (50.6±11.6)%, (49.9±9.3) %,and(35.4±7.0)% and the swimming distance percentages of 20%marginal area were (46.4 ± 7.3 ) %, ( 11.6 ± 3.9) %, ( 14.4 ± 2. 6) %, and (25.8 ± 3.3)%. The mice in three experiment groups showed increase in the times of passing through platform point, swimming distance percentage of the first quadrant, and decrease in distance percentage of 20% marginal area compared with control group. The results in three experiment groups were no significantly different( P ＜ 0. 05).CONCLUSION: Immunization with A342 and its subunits can effectively ameliorate impairment of spatial learning and memory in APPSWE transgenic mice.