全身振动可改善hAPP转基因小鼠海马神经胶质病理改变,但不影响斑块负荷。

IF 4.7 2区 心理学 Q1 BEHAVIORAL SCIENCES Behavioral and Brain Functions Pub Date : 2023-03-20 DOI:10.1186/s12993-023-00208-9
Tamas Oroszi, Eva Geerts, Reuben Rajadhyaksha, Csaba Nyakas, Marieke J G van Heuvelen, Eddy A van der Zee
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引用次数: 0

摘要

背景:阿尔茨海默病(AD)是老年痴呆症的核心病因。AD的主要特征之一是与胶质介导的神经炎症相关的细胞外淀粉样蛋白(Aβ)积累(app病理)。全身振动(WBV)是一种被动的运动形式,但其对AD病理的影响尚不清楚。方法:采用5月龄雄性J20小鼠(26只)和野生型(WT)仔鼠(24只),观察WBV对脑组织淀粉样蛋白病理及正常脑组织的影响。J20和WT小鼠均在振动平台或伪振动处理下进行WBV。振动干预包括每天10分钟的2次WBV疗程,每周5天,连续5周。5周WBV后,用平衡木测试来评估运动表现。采集脑组织,定量测定星形胶质细胞和小胶质细胞的Aβ沉积和免疫标志物。结果:在这个相对年轻的年龄,J20小鼠的斑块数量有限。淀粉样斑块负荷不受白细胞白蛋白的影响。基于iba1免疫染色的小胶质细胞激活在J20小鼠中与WT小鼠相比显著增加,而CD68的表达没有显著改变。WBV治疗能有效改善J20和WT动物齿状回小胶质细胞的激活,但在其他亚区没有效果。此外,基于覆盖率的GFAP表达在J20伪处理小鼠中与WT窝群相比有所降低,并且在J20 WBV与伪处理动物中显著保留。此外,与伪振动组相比,WBV组仅对WT动物有改善运动表现的趋势。结论:与文献一致,我们发现J20小鼠在~ 6月龄时斑块负荷较早,GFAP表达降低,小胶质细胞活性增加。我们的研究结果表明,WBV对脑病理的早期进展有有益的影响。最重要的是,WBV将GFAP阳性星形胶质细胞的形态恢复到WT水平,这可以被认为是非病理性的,因此是“健康”的水平。下一步的实验需要确定WBV是否对老年J20小鼠或其他AD小鼠模型也有影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Whole-body vibration ameliorates glial pathological changes in the hippocampus of hAPP transgenic mice, but does not affect plaque load.

Background: Alzheimer's disease (AD) is the core cause of dementia in elderly populations. One of the main hallmarks of AD is extracellular amyloid beta (Aβ) accumulation (APP-pathology) associated with glial-mediated neuroinflammation. Whole-Body Vibration (WBV) is a passive form of exercise, but its effects on AD pathology are still unknown.

Methods: Five months old male J20 mice (n = 26) and their wild type (WT) littermates (n = 24) were used to investigate the effect of WBV on amyloid pathology and the healthy brain. Both J20 and WT mice underwent WBV on a vibration platform or pseudo vibration treatment. The vibration intervention consisted of 2 WBV sessions of 10 min per day, five days per week for five consecutive weeks. After five weeks of WBV, the balance beam test was used to assess motor performance. Brain tissue was collected to quantify Aβ deposition and immunomarkers of astrocytes and microglia.

Results: J20 mice have a limited number of plaques at this relatively young age. Amyloid plaque load was not affected by WBV. Microglia activation based on IBA1-immunostaining was significantly increased in the J20 animals compared to the WT littermates, whereas CD68 expression was not significantly altered. WBV treatment was effective to ameliorate microglia activation based on morphology in both J20 and WT animals in the Dentate Gyrus, but not so in the other subregions. Furthermore, GFAP expression based on coverage was reduced in J20 pseudo-treated mice compared to the WT littermates and it was significantly reserved in the J20 WBV vs. pseudo-treated animals. Further, only for the WT animals a tendency of improved motor performance was observed in the WBV group compared to the pseudo vibration group.

Conclusion: In accordance with the literature, we detected an early plaque load, reduced GFAP expression and increased microglia activity in J20 mice at the age of ~ 6 months. Our findings indicate that WBV has beneficial effects on the early progression of brain pathology. WBV restored, above all, the morphology of GFAP positive astrocytes to the WT level that could be considered the non-pathological and hence "healthy" level. Next experiments need to be performed to determine whether WBV is also affective in J20 mice of older age or other AD mouse models.

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来源期刊
Behavioral and Brain Functions
Behavioral and Brain Functions 医学-行为科学
CiteScore
5.90
自引率
0.00%
发文量
11
审稿时长
6-12 weeks
期刊介绍: A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.
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