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孕期母体游泳锻炼通过Wnt/β-连环蛋白通路增强神经发生并抑制自闭症小鼠的细胞凋亡来改善记忆。

Maternal Swimming Exercise During Pregnancy Improves Memory Through Enhancing Neurogenesis and Suppressing Apoptosis via Wnt/β-Catenin Pathway in Autistic Mice.

作者信息

Park Sang-Seo, Kim Chang-Ju, Kim Seong-Hyun, Kim Tae-Woon, Lee Sam-Jun

机构信息

Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.

School of Health and Kinesiology, University of Nebraska at Omaha, Omaha, NE, USA.

出版信息

Int Neurourol J. 2021 Nov;25(Suppl 2):S63-71. doi: 10.5213/inj.2142338.169. Epub 2021 Nov 30.

Abstract

PURPOSE

Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway.

METHODS

On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out.

RESULTS

Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups.

CONCLUSION

Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.

摘要

目的

Wnt信号通路与认知功能相关的神经发育过程密切相关。给怀孕小鼠注射丙戊酸后,研究怀孕小鼠游泳运动对幼崽记忆、神经元生成和凋亡的影响,并探讨其与Wnt/β-连环蛋白信号通路的关系。

方法

在怀孕第12天,给小鼠皮下注射400mg/kg丙戊酸。对照组怀孕小鼠游泳运动组和丙戊酸注射后游泳运动组的怀孕小鼠,每天游泳1次,每次30分钟,每周重复5天,持续3周。进行用于记忆功能的穿梭箱回避任务和莫里斯水迷宫任务、针对5-溴-2'-脱氧尿苷(BrdU)阳性细胞的免疫组织化学以及针对脑源性神经营养因子(BDNF)、Wnt、β-连环蛋白、Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤2(Bcl-2)、裂解的半胱天冬酶-3的蛋白质印迹分析。

结果

孕期母体游泳运动改善了丙戊酸注射幼崽的记忆功能,增加了BDNF表达和神经元增殖。孕期母体游泳运动抑制了丙戊酸注射幼崽中Wnt表达和β-连环蛋白的磷酸化。孕期母体游泳运动抑制了丙戊酸注射幼崽中Bax和裂解的半胱天冬酶-3的表达,并增加了Bcl-2表达。

结论

孕期母体游泳运动通过激活Wnt/β-连环蛋白信号级联反应增加细胞增殖并抑制凋亡,从而改善了丙戊酸注射幼崽的记忆功能。孕期母体游泳运动可能对诱导胎儿患自闭症的因素具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/8654312/0d14792a0ea8/inj-2142338-169f1.jpg

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