Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers

Abstract

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers. Thirteen of these markers displayed augmented levels in patients compared to CBD. Twenty-one markers correlated with the age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients, as was the average plasma GABA concentration. GABA modulated the release of seven cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) from the patients. The study reveals significant changes in the plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.

GABAB-Receptor Agonist-Based Immunotherapy for Type 1 Diabetes in NOD Mice

“…In contrast to murine immune cells, the expression patterns of GABBR1 and GABBR2 in human APC and T cells as determined by RNA-Seq were highly skewed, with relatively high expression of GABBR1 (particularly in B cells, DCs, and monocytes), but little or no detectable GABBR2 expression ( Figure 4 and Supplementary Table S1 ). Consistent with these RNA-Seq data, GABBR1 , but not GABBR2 , was detected in human PBMCs by RT-qPCR [ 64 ]. To reconcile these findings with the functional evidence of GABA B -R-mediated modulation of human APCs noted above, it is possible that low levels of GABBR2 are sufficient to form GABA B -Rs that modulate APC functions or that the GABBR1 subunit on its own has some intracellular activity as previously reported [ 65 , 66 , 67 ].…”

“…In contrast to the relatively high level of ρ 2 transcripts detected in human APCs and B cells, human T cells express only low levels of the ρ 2 subunit. These RNA-Seq gene expression profiles of human immune cells have some overlaps, as well as some contrasts, with the results obtained using RT-qPCR methods [ 4 , 6 , 9 , 64 , 72 ]. Since the RNA-Seq data were obtained using a different technology that is highly quantitative and allows cross-comparison of gene expression levels within a single sample, the presented gene expression profiles provide an alternative resource to help guide hypothesis generation and future research.…”

GABAergic Mechanisms Can Redress the Tilted Balance between Excitation and Inhibition in Damaged Spinal Networks

“…The peak of GABA after SCI originates from not only the destruction of the membrane of GABAergic and glia cells but also the synaptic release at the site of injury [99] facilitated by spreading depolarization along the injured tissue [100]. The contribution of circulating GABA leaking through the impaired blood-spinal barrier is probably a minor one as GABA concentrations in the plasma [101,102] are far below the ones found at the lesion site. Nevertheless, there might be enough GABA to activate highly sensitive extra-synaptic GABA receptors such as the ones incorporating the δ subunit [40].…”

Activation of GABA(A) receptors inhibits T cell proliferation

“…Having established the expression of multiple GABA(A)R subunits in mouse and human T cells, we next wished to assess their functionality. The difficulty in assessing the direct action of GABA on immune cells lies in the fact that GABA is present in the blood at variable concentrations (usually 100-500nM depending on health status, age and sex) [ 24 – 26 ]. Therefore, while some reports show a direct action of GABA or the GABA(A)R agonist muscimol on immune cells [ 15 ] others do not [ 14 ].…”

“…GABA on immune cells lies in the fact that GABA is present in the blood at variable concentrations (usually 100-500nM depending on health status, age and sex) [24][25][26]. Therefore, while some reports show a direct action of GABA or the GABA(A)R agonist muscimol on immune cells [15] others do not [14].…”