Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Acta Physiol (Oxf). 2015 Mar;213(3):575-85. doi: 10.1111/apha.12440. Epub 2015 Jan 21.
The concept of nerve-driven immunity recognizes a link between the nervous and the immune system. γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain, and receptors activated by GABA can be expressed by immune cells. Here, we examined whether the expression of GABA receptors and chloride transporters in human peripheral blood mononuclear cells (PBMCs) was influenced by gender, pregnancy or mental health.
We used RT-qPCR to determine the mRNA expression level in PBMCs from men (n = 16), non-pregnant women (n = 19), healthy pregnant women (n = 27) and depressed pregnant women (n = 15).
The ρ2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The δ and ρ2 subunits were up-regulated by pregnancy, whereas the ε subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in turn, commonly expressed the α6 and the γ2 subunits. The β1 and ε subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women, while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs.
The results demonstrate the impact gender, pregnancy and mental health have on the expression of GABA receptors and chloride transporters expressed in human PBMCs.
神经驱动免疫的概念认识到神经系统和免疫系统之间的联系。γ-氨基丁酸(GABA)是大脑中的主要抑制性神经递质,GABA 激活的受体可以在免疫细胞中表达。在这里,我们研究了人类外周血单核细胞(PBMC)中 GABA 受体和氯离子转运体的表达是否受性别、妊娠或心理健康的影响。
我们使用 RT-qPCR 确定了来自男性(n=16)、未怀孕女性(n=19)、健康孕妇(n=27)和抑郁孕妇(n=15)的 PBMC 中的 mRNA 表达水平。
ρ2 亚基在所有样本中的 GABA-A 受体亚基表达水平最为突出。δ和ρ2 亚基受妊娠上调,而ε亚基在健康孕妇中的表达更为常见,而非怀孕女性中则常见表达α6 和γ2 亚基。β1 和ε 亚基的表达在孕妇中受到抑郁的影响。GABA-B1 受体在孕妇抑郁中上调,而 NKCC1 和 KCC4 转运体在妊娠时下调。mRNA 表达水平的变化表明 GABA 受体参与了妊娠中的耐受建立和维持。重要的是,心理健康与特定受体亚基表达之间的相关性揭示了免疫细胞与大脑之间的联系。PBMC 中可能存在心理健康的生物标志物。
这些结果表明,性别、妊娠和心理健康对人类 PBMC 中 GABA 受体和氯离子转运体的表达有影响。