Birnir, B. | Search bioRxiv

bioRxiv2019

Depression, GABA and age correlate with the plasma levels of inflammatory markers.

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined if levels of immunological protein markers altered with depression, age or by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Analysis of plasma samples from patients with major depressive episode and control blood donors (CBD) revealed expression of 67 inflammatory markers. Thirteen of these markers had augmented levels in patients as compared to CBD. and 21 markers correlated with 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 in the 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 and so was the average plasma GABA concentration. GABA modulated release of seven cytokines in CD3+ stimulated peripheral blood mononuclear cells (PBMC) from the patients. The study reveals significant changes in plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.

pathology↗

bioRxiv2019

GABAA receptor-mediated currents and hormone mRNAs in cells expressing more than one hormone transcript in intact human pancreatic islets

In pancreatic islets the major cell-types are , {beta} and {delta} cells, secreting the hormones glucagon (GCG), insulin (INS) and somatostatin (SST), respectively. The GABA ({gamma}-aminobutyric acid) signalling system is expressed in human pancreatic islets. We have previously used single-cell RT-PCR in combination with current recordings to correlate expression of single hormone transcript with functional GABAA receptor (iGABAAR) properties in islets. Here we extended these studies to islet cells from non-diabetic and type 2 diabetic donors that express mRNAs for more than one hormone. We detected cells expressing double (/{beta}, /{delta}, {beta}/{delta} cell-types) and triple (/{beta}/{delta} cell-type) hormone transcripts. The most common mixed-identity cell-type was the /{beta} group where the cells could be grouped into {beta}- and -like subgroups. The {beta}-like cells had low GCG/INS expression ratio (< 0.6) and significantly higher frequency of single-channel iGABAAR openings than the -like cells where the GCG/INS expression ratio was high (> 1.2). The difference in expression levels and single channel iGABAAR characteristics varied in the /{beta}/{delta} cell-type. No correlation was observed between the cell-types identity with time in culture or cell size. Clearly, multiple hormone transcripts can be expressed in islet cells whereas iGABAAR functional properties appear or {beta} cell specific.

cell biology↗