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经过培育具有低内在有氧运动能力的大鼠将肥胖与大脑炎症和海马体结构可塑性降低联系起来。

Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus.

机构信息

Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland.

Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland; Department of Psychology, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland.

出版信息

Brain Behav Immun. 2021 Oct;97:250-259. doi: 10.1016/j.bbi.2021.06.017. Epub 2021 Jul 2.

DOI:10.1016/j.bbi.2021.06.017
PMID:34224822
Abstract

BACKGROUND

Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats.

METHODS

We examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins.

RESULTS

Our study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones.

CONCLUSION

Our study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.

摘要

背景

越来越多的证据表明,肥胖和代谢健康状况不佳与认知能力下降有关,但其中的机制联系尚未得到解决。我们选择了天生有氧能力低和高的两种大鼠进行研究,以测试低身体适应性、肥胖遗传易感性与大脑健康之间的关联。我们假设,与身体适应性更高的高能力跑步者(HCR)大鼠相比,具有更高肥胖水平的低能力跑步者(LCR)大鼠的海马体炎症会增加,并且其可塑性会降低。

方法

我们研究了 LCR 大鼠和 HCR 大鼠的海马体中的炎症和脑可塑性标志物,并对其进行了比较。通过研究年轻(8 周)和老年(40 周)大鼠,确定了年龄的影响。我们使用蛋白质印迹和免疫组织化学来定量目标蛋白的表达。

结果

我们的研究表明,在年轻时,LCR 大鼠海马体中的成年新生神经元数量明显低于 HCR 大鼠,而且随着年龄的增长,这种差异变得更加明显。年轻动物的突触蛋白表达相对较高,而老年动物的表达则较低。与 HCR 大鼠相比,LCR 大鼠的大脑炎症程度更高,并且在老年大鼠中更为明显。

结论

我们的研究首次表明,与肥胖和代谢健康状况不佳相关的低内在有氧适应性也与年轻时海马体结构可塑性降低有关。我们的结果还表明,大脑炎症可能是肥胖和认知能力下降之间联系的一个因素。

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