有氧运动对睡眠剥夺大鼠学习记忆及海马神经元突触可塑性的效果

doi:10.3969/j.issn.1006-9771.2022.11.006

《中国康复理论与实践》 ›› 2022, Vol. 28 ›› Issue (11): 1270-1277.doi: 10.3969/j.issn.1006-9771.2022.11.006

有氧运动对睡眠剥夺大鼠学习记忆及海马神经元突触可塑性的效果

李童¹,方志鹏²,邵玉萍²(),王平³

1.湖北中医药大学基础医学院，湖北武汉市 430065
2.湖北中医药大学体育健康学院，湖北武汉市 430065
3.湖北中医药大学老年医学研究所，湖北武汉市 430065

收稿日期:2022-10-29 修回日期:2022-11-03 出版日期:2022-11-25 发布日期:2022-12-20
通讯作者: 邵玉萍 E-mail:1146042812@qq.com
作者简介:李童(1996-)，男，汉族，湖北随州市人，硕士研究生，主要研究方向：老年病防治理论及临床应用。|邵玉萍(1972-)，女，汉族，湖北仙桃市人，教授，主要研究方向：老年病防治与传统运动养生研究。
基金资助:
科技部重点研发计划项目(2018YFC1705600)

Effect of aerobic exercise on learning and memory, and synaptic plasticity of hippocampal neurons for sleep-deprived rats

LI Tong¹,FANG Zhipeng²,SHAO Yuping²(),WANG Ping³

1. School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China
2. School of Physical and Health Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China
3. Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China

Received:2022-10-29 Revised:2022-11-03 Published:2022-11-25 Online:2022-12-20
Contact: SHAO Yuping E-mail:1146042812@qq.com
Supported by:
National Key R & D Program of China(2018YFC1705600)

摘要/Abstract

摘要：

目的探讨有氧运动对睡眠剥夺大鼠定位巡航活动和空间探索活动，海马区神经元形态，海马神经元树突棘密度、突触相关蛋白，以及海马区环磷酸腺苷反应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路的影响。

方法 Sprague-Dawley大鼠48只，随机分为对照组、模型组、模型运动组和运动组，每组12只。模型运动组和运动组采用动物跑台进行有氧运动4周。运动干预结束后，模型组和模型运动组采用多平台水环境连续睡眠剥夺72 h。Morris水迷宫评估各组定位巡航活动和空间探索活动表现，运用HE染色和高尔基染色法评估神经元细胞树突棘形态及其密度，Western blotting检测海马突触后致密蛋白95 (PSD95)、突触素(SYN)、生长相关蛋白43(GAP43)、Rac1、BDNF、p-CREB和CREB表达。

结果与对照组相比，模型组平台潜伏期和游泳总距离增加(P < 0.05)，穿越平台次数、目标象限停留时间和距离减少(P < 0.05)，海马CA1区神经元排列紊乱，单位长度树突棘总密度以及成熟型、不成熟型、丝状伪足型树突棘密度下降(P < 0.05)，PSD95、SYN、GAP43、Rac1、BDNF、p-CREB和CREB蛋白表达降低(P < 0.05)；与模型组相比，模型运动组平台潜伏期和游泳总距离降低(P < 0.05)，穿越平台次数、目标象限停留时间和距离增加(P < 0.05)，海马CA1区神经元数量增加，排列整齐，单位长度树突棘总密度以及成熟型、不成熟型、丝状伪足型树突棘密度增加(P < 0.05)，PSD95、SYN、GAP43、Rac1、BDNF、p-CREB和CREB蛋白表达增加(P < 0.05)。

结论有氧运动能够缓解睡眠剥夺大鼠学习记忆损伤，可能与调控海马CREB/BDNF信号通路，改善突触可塑性有关。

关键词: 睡眠剥夺, 有氧运动, 突触可塑性, 学习记忆, 大鼠

Abstract:

Objective To investigate the effects of aerobic exercise on sleep-deprived rats positioning cruise and space exploration activities, synaptic mechanism, involving hippocampal neuron morphology, dendritic spine density, synaptic related proteins and cyclic adenosine phosphate reactive element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway.

Methods A total of 48 Sprague-Dawley rats were randomly divided into control group (n = 12), model group (n = 12), model-exercise group (n = 12) and exercise group (n = 12). The model-exercise group and the exercise group accepted aerobic exercise with treadmill for four weeks. After exercise intervention, the model group and the model-exercise group were continuously deprived sleep for 72 hours with a multi-platform water environment. They were assessed with Morris Water Maze of positioning cruise and space exploration. The morphology and density of dendritic spines in hippocampal neurons were observed with HE staining and Golgi staining. The expression of hippocampal proteins of postsynaptic density protein 95 (PSD95), synapsin (SYN), growth-associated protein 43 (GAP43), Rac1, BDNF, p-CREB and CREB were measured with Western blotting.

Results Compared with the control group, the latency and the total swimming distance increased in the model group (P< 0.05); the number of crossing the platform, the target quadrant residence time and distance decreased (P< 0.05); the neurons in the hippocampal CA1 region were disordered, the total density of dendritic spines per unit length and the density of mature, immature and filamentous pseudopodia dendritic spines decreased (P< 0.05); and the expression of PSD95, SYN, GAP43, Rac1, BDNF, p-CREB and CREB decreased (P< 0.05). Compared with the model group, the latency and total swimming distance of the model-exercise group decreased (P< 0.05); the target quadrant residence time and distance increased (P< 0.05); the number of neurons in the hippocampal CA1 region increased and arranged neatly; the total density of dendritic spines per unit length and the density of mature, immature and filamentous pseudopod dendritic spines increased (P< 0.05); and the expression of PSD95, SYN, GAP43, Rac1, BDNF, p-CREB and CREB increased (P< 0.05).

Conclusion Aerobic exercise can alleviate the learning and memory impairment of sleep-deprived rats, which may relate to the regulation of CREB/BDNF signaling pathway in hippocampus for improvement of synaptic plasticity.

Key words: sleep deprivation, aerobic exercise, synaptic plasticity, learning and memory, rats

中图分类号:

李童,方志鹏,邵玉萍,王平. 有氧运动对睡眠剥夺大鼠学习记忆及海马神经元突触可塑性的效果[J]. 《中国康复理论与实践》, 2022, 28(11): 1270-1277.

LI Tong,FANG Zhipeng,SHAO Yuping,WANG Ping. Effect of aerobic exercise on learning and memory, and synaptic plasticity of hippocampal neurons for sleep-deprived rats[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(11): 1270-1277.

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组别	n	潜伏期/s	游泳总距离/cm	穿越平台次数/次	目标象限距离/cm	目标象限时间/s
对照组	12	26.39±9.33	376.32±42.78	4.41±0.70	419.97±42.18	29.69±3.09
模型组	12	51.18±12.46^a	586.02±51.79^a	1.82±0.59^a	323.84±44.47^a	21.38±1.88^a
模型运动组	12	32.20±7.14^b	493.53±42.68^b	3.49±0.82^b	365.73±19.63^b	26.09±2.06^b
运动组	12	22.16±9.66	361.25±33.21	4.86±0.81	443.36±39.04	32.48±2.49
F值		17.303	56.723	36.492	22.514	40.907
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

组别	n	总密度	成熟型	不成熟型	丝状伪足型
对照组	6	15.63±1.77	7.82±0.88	6.25±0.71	1.71±0.13
模型组	6	8.04±0.92^a	2.49±0.27^a	4.02±0.46^a	1.36±0.15^a
模型运动组	6	12.53±1.10^b	5.03±0.44^b	4.64±0.41^b	1.56±0.18^b
运动组	6	17.14±1.34	8.57±0.67	6.86±0.54	1.88±0.13
F值		72.976	170.371	49.148	16.417
P值		< 0.001	< 0.001	< 0.001	< 0.001

组别	n	PSD95	SYN1	GAP43	Rac1
对照组	6	61.57±2.99	57.25±3.76	54.88±3.77	51.02±1.97
模型组	6	38.11±2.29^a	34.61±2.06^a	31.60±1.57^a	41.05±2.32^a
模型运动组	6	56.01±3.45^b	42.82±2.87^b	44.20±2.74^b	44.61±2.92^b
运动组	6	72.06±3.58	61.97±2.56	62.13±2.87	53.08±2.95
F值		62.189	58.118	65.320	42.865
P值		< 0.001	< 0.001	< 0.001	< 0.001

组别	n	BDNF	p-CREB	CREB
对照组	6	90.59±1.54	35.49±4.36	62.13±2.69
模型组	6	79.97±1.39^a	7.47±1.03^a	42.55±3.19^a
模型运动组	6	84.46±1.93^b	22.44±3.16^b	53.54±3.29^b
运动组	6	94.47±2.02	41.18±3.02	63.86±2.63
F值		41.037	68.771	26.700
P值		< 0.001	< 0.001	< 0.001

有氧运动对睡眠剥夺大鼠学习记忆及海马神经元突触可塑性的效果

Effect of aerobic exercise on learning and memory, and synaptic plasticity of hippocampal neurons for sleep-deprived rats

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