Roles of sodium channel-voltage-gated-beta 2B in learning and memory improvements of transgenic mice with Alzheimer's disease
10.3760/cma.j.cn371468-20201216-00069
- VernacularTitle:电压门控性钠离子通道2B对阿尔茨海默病模型小鼠学习记忆功能的作用
- Author:
Shan LI
1
;
Haoran ZHAO
;
Yaxin TAN
;
Yanbin XIYANG
Author Information
1. 昆明医科大学基础医学院神经科学研究所 650500
- Keywords:
Alzheimer's disease;
Sodium-channel-voltage-beta 2B;
Amyloid precursor protein;
Cognitive dysfunction;
Transgenic mice
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2021;30(6):489-496
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the potential role of amyloid precursor protein (APP) in the sodium-channel-voltage-beta 2B (SCN2B)-mediated improvement of memory and cognitive function in Alzheimer's Disease (AD).Methods:The SCN2B gene knockout mice (SCN2B -/-) were hybridized with APP gene knockout mice (APP -/-), APP gene heterozygous mice (APP +/-) and APP gene transgenic mice (APP +/+), and the tail tissue of the same mouse was genotyped by PCR gene detection.The mice were divided into SCN2B -/-APP -/- group, SCN2B -/-APP +/- group and SCN2B -/-APP +/+ group.The C57BL/6 wild-type mice were Wild type (WT) group, with 9 mice in each group.SCN2B -/-APP -/-, SCN2B -/-APP +/-, SCN2B -/-APP +/+ transgenic mice and the wild-type mice at the age of 6 months, 12 months, and 18 months were tested by Morris water Maze and Y maze test to detect the cognitive function between each group.Meanwhile, SCN2B -/-APP -/-, SCN2B -/-APP +/-, SCN2B -/-APP +/+ transgenic mice aged 6, 12, 18 months and age-match wild-type were selected to detect neuronal processes in hippocampal CA1 region, and the number of neuronal processes in basal and distal regions of hippocampal CA1 region was quantitatively analyzed.SPSS 21.0 statistical software was used for data statistics and analysis.The differences between the two groups were compared and analyzed by independent-sample t test, the comparison between multiple groups was analyzed by one way analysis of variance (ANOVA), and repeated measurement ANOVA was used to analyze behavioral deta. Results:Repeated measurement ANOVA was used to analyze the data of water maze test. The data showed that the interaction effect of escape latency group and time was significant in 18 month old mice ( Ftime×group=3.63, P<0.01). Simple effect analysis showed that compared with SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the escape latency of mice in SCN2B -/-APP +/+ group was significantly prolonged from day 4 to 6 (4th day: (47.00±2.00)s, (43.11±1.96) s, (41.89±3.06)s, t=-4.16, 1.00, both P<0.05; 5th day: (45.22±2.54) s, (36.33±2.78) s, (37.00±2.45)s, t=-7.08, -0.54, both P<0.05; 6th day: (38.11±2.03)s, (34.11±2.32)s, (33.00±2.91)s, t=-3.90, 0.90, both P<0.05). The residence time in the target quadrant was shortened((18.00±1.73)s, (25.56±1.33)s, (24.33 ±1.94)s; t=10.37, 1.56, both P<0.05). (2) Y-maze results showed that compared with SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the number of novel arm entry in 18 month old mice in SCN2B -/-APP +/+ group was decreased((50.22±3.68), (57.22±3.74), (58. 44±5.14) ; t=3.40, -0.48, both P<0.05), and the residence time of stay in the new arm was reduced((10.89±0.62)min, (14.33±0.59)min, (13.89±0.74)min; t= 8.16, 0.44, both P<0.05), and the distance of movement in the new arm was significantly reduced ((37.26±2.01)m , (45.67±2.45)m , (46.11±3.27)m ; t=7.81, 0.91, both P<0.05). (3) Golgi staining showed that SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the number of apical dendrites in hippocampal neurons of 18 month old mice in SCN2b -/-App +/+ group(number of apical dendrites: (1.78±0.37), (3.67±0.81), (3.00±1.21); t=3.36, 1.41, both P<0.05) and the number of basal dendrites (the number of basal dendrites: (1.11±0.50), (3.11±0.50), (2.56±0.69); t=4.06, 1.21, both P<0.05). Conclusion:SCN2B knockdown can improve the ability of spatial learning and memory in aged mice.Overexpression of APP can partially offset the improvement of cognitive function caused by SCN2B knockdown, and may be affected by the number of basal and distal processes of neurons in the hippocampal CA1 region of the mice.
