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首页> 外文期刊>Genes, brain, and behavior >Strain-dependent variations in visceral sensitivity: relationship to stress, anxiety and spinal glutamate transporter expression
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Strain-dependent variations in visceral sensitivity: relationship to stress, anxiety and spinal glutamate transporter expression

机译:内脏敏感性的应变依赖性变化:与压力,焦虑和脊髓谷氨酸转运蛋白表达的关系

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摘要

Responses to painful stimuli differ between populations, ethnic groups, sexes and even among individuals of a family. However, data regarding visceral pain are still lacking. Thus, we investigated differences in visceral nociception across inbred and outbred mouse strains using colorectal distension. Anxiety and depression-like behaviour were assessed using the open field and forced swim test as well as the corticosterone stress response. Possible mechanistic targets [excitatory amino acid transporter (EAAT-1), brain-derived neurotrophic factor (BDNF) and 5HT1A receptor] were also assessed using quantitative real-time polymerase chain reaction. Adult, male, inbred and outbred mouse strains were used in all assays (inbred strains; CBA/J Hsd, C3H/HeNHsd, BALB/c OlaHsd, C57 BL/6JOlaHsd, DBA/2J RccHsd, CAST/EiJ, SM/J, A/J OlaHsd, 129P2/OlaHsd, FVB/NHan Hsd and outbred strains: Swiss Webster, CD-1). mRNA expression levels of EAAT-1, BDNF and 5HT1A receptor (HTR1A) were quantified in the lumbosacral spinal cord, amygdala and hippocampus. A significant effect of strain was found in visceral sensitivity, anxiety and depressive-like behaviours. Strain differences were also seen in both baseline and stress-induced corticosterone levels. CBA/J mice consistently exhibited heightened visceral sensitivity, anxiety behaviour and depression-like behaviour which were associated with decreased spinal EAAT-1 and hippocampal BDNF and HTR1A. Our results show the CBA/J mouse strain as a novel mouse model to unravel the complex mechanisms of brain-gut axis disorders such as irritable bowel syndrome, in particular the underlying mechanisms of visceral hypersensitivity, for which there is great need. Furthermore, this study highlights the importance of genotype and the consequences for future development of transgenic strains in pain research.
机译:人口,种族,性别,甚至家庭成员对疼痛刺激的反应也不同。但是,仍然缺乏有关内脏痛的数据。因此,我们调查了使用结直肠扩张的近交和近交小鼠品系内脏伤害感受的差异。使用开放视野和强迫游泳测试以及皮质酮应激反应评估焦虑和抑郁样行为。还使用定量实时聚合酶链反应评估了可能的机制靶标[兴奋性氨基酸转运蛋白(EAAT-1),脑源性神经营养因子(BDNF)和5HT1A受体]。成年,雄性,近交和近交小鼠品系均用于所有测定(近交品系; CBA / J Hsd,C3H / HeNHsd,BALB / c OlaHsd,C57 BL / 6JOlaHsd,DBA / 2J RccHsd,CAST / EiJ,SM / J, A / J OlaHsd,129P2 / OlaHsd,FVB / NHan Hsd和近交菌株:Swiss Webster,CD-1)。定量在腰s脊髓,杏仁核和海马体中EAAT-1,BDNF和5HT1A受体(HTR1A)的mRNA表达水平。在内脏敏感性,焦虑和抑郁样行为中发现了应变的显着效果。在基线和压力诱导的皮质酮水平上也发现了应变差异。 CBA / J小鼠始终表现出较高的内脏敏感性,焦虑行为和抑郁样行为,这与脊髓EAAT-1和海马BDNF和HTR1A降低有关。我们的结果表明,CBA / J小鼠品系是一种新颖的小鼠模型,可揭示诸如肠易激综合征等脑-肠轴疾病的复杂机制,尤其是内脏超敏性的潜在机制,对此非常需要。此外,该研究突出了基因型的重要性以及转基因菌株在疼痛研究中对未来发展的影响。

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