Winther Gudrun, Pyndt Jørgensen Betina M, Elfving Betina, Nielsen Denis Sandris, Kihl Pernille, Lund Sten, Sørensen Dorte Bratbo, Wegener Gregers
1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Skovagervej 2,DK-8240 Risskov,Denmark.
2Section of Experimental Animal Models,Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,University of Copenhagen,Thorvaldsensvej 57,DK-1871 Frederiksberg C,Denmark.
Acta Neuropsychiatr. 2015 Jun;27(3):168-76. doi: 10.1017/neu.2015.7. Epub 2015 Feb 18.
Gut microbiota (GM) has previously been associated with alterations in rodent behaviour, and since the GM is affected by the diet, the composition of the diet may be an important factor contributing to behavioural changes. Interestingly, a magnesium restricted diet has been shown to induce anxiety and depressive-like behaviour in humans and rodents, and it could be suggested that magnesium deficiency may mediate the effects through an altered GM.
The present study therefore fed C57BL/6 mice with a standard diet or a magnesium deficient diet (MgD) for 6 weeks, followed by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated to the behaviour and hippocampal markers.
It was found that mice exposed to MgD for 6 weeks were more immobile than control mice in the FST, suggesting an increased depressive-like behaviour. No significant difference was detected in the GTT. GM composition correlated positively with the behaviour of undisturbed C57BL/6 mice, feeding MgD diet altered the microbial composition. The altered GM correlated positively to the hippocampal interleukin-6.
In conclusion, we hypothesise that imbalances of the microbiota-gut-brain axis induced by consuming a MgD diet, contributes to the development of depressive-like behaviour.
肠道微生物群(GM)先前已被证明与啮齿动物行为改变有关,并且由于GM会受到饮食的影响,饮食组成可能是导致行为变化的一个重要因素。有趣的是,已表明镁限制饮食会在人类和啮齿动物中诱发焦虑和抑郁样行为,并且可以推测镁缺乏可能通过改变的GM来介导这些影响。
因此,本研究给C57BL/6小鼠喂食标准饮食或缺镁饮食(MgD)6周,随后在强迫游泳试验(FST)中进行行为测试以评估抑郁样行为。在FST后2天进行腹腔内葡萄糖耐量试验(GTT)以评估代谢改变。从海马体分析神经炎症标志物。分析GM组成并将其与行为和海马体标志物相关联。
发现暴露于MgD 6周的小鼠在FST中比对照小鼠更不动,表明抑郁样行为增加。在GTT中未检测到显著差异。GM组成与未受干扰的C57BL/6小鼠的行为呈正相关,喂食MgD饮食会改变微生物组成。改变的GM与海马白细胞介素-6呈正相关。
总之,我们假设食用MgD饮食引起的微生物群-肠道-脑轴失衡会导致抑郁样行为的发展。