Search bioRxivSearch

bioRxiv · 10.1101/689984

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

Abstract

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.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bhandage, A. K., Cunningham, J. L., Jin, Z., Shhen, Q., Bongiovanni, S., Korol, S. V., Syk, M., Kamali-Moghaddam, M., Ekselius, L., Birnir, B.. 2019-07-02. Depression, GABA and age correlate with the plasma levels of inflammatory markers.. https://doi.org/10.1101/689984

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology

Impact of Rigid Gas Permeable Contact Lenses Removal on Anterior and Posterior Corneal Surfaces in Keratoconus Patients

PurposeTo evaluate the impact of removal of rigid gas-permeable (RGP) contact lenses on the anterior and posterior cornea surfaces of eyes with keratoconus.\n\nMethodsEight eyes of 8 patients with keratoconus (KC) (age 34.3 {+/-} 15.3 years; range 19-60 years) were enrolled. Anterior segment optical coherence tomography (AS-OCT) was performed at 1, 5, 10, 20, and 60 minutes after the patients removed their RGP contact lenses. Measurements included anterior and posterior best-fit sphere (BFS); elevation values and corneal surface areas; corneal thickness at the thinnest point; and the anterior-posterior ratio of the corneal surface (As/Ps) between 1 minute and 60 minutes after RGP contact lens removal.\n\nResultsAnterior and posterior elevation values and corneal surface areas showed significant increases, whereas anterior and posterior BFS and central corneal thickness decreased significantly (P < 0.01) between 1 minute and 60 minutes after RGP contact lens removal. No statistically significant differences were found in the As/Ps ratio during the first hour after suspending RGP contact lens wear.\n\nConclusionsWe found that the patients with keratoconus experienced significant changes in both the anterior and posterior corneal shape for 60 minutes after removal of RGP contact lenses.

pathology

Dynamic healing and remodeling of mandibular ramus in segmental mobility and cortical overlap after intraoral vertical osteotomy

The ramus immediately after intraoral vertical ramus osteotomy (IVRO) shows segmental mobility, cortical overlap, and projection, which yield smooth-surfaced continuity and stability after one year. This study aimed to elucidate the three-dimensional (3D) morphological changes driven by regional healing and remodeling 12 months postoperatively (Post) and their relationships with the immediate postoperative (Imm) segmental overlapping pattern. We performed a retrospective study of the morphological change of mandibular ramus in terms of time and amount of cortical overlap after IVRO. 3D computed tomography data of 108 hemi-mandibles were analyzed by independent superimposition of Imm proximal and distal segment to Post mandible. Analysis showed extensive regional bone resorption and apposition resulting in a relatively flat-surfaced and morphologically intact Post ramus. The middle ramal remodeling was significantly associated with Imm overlapping patterns and Post mandibular movement, new bony projections of various shapes being observed at the posterior border of the Post ramus. The ramus after IVRO underwent dynamic morphological changes during healing/remodeling which were partly associated with Imm overlap. Moreover, the Post functional and smooth-surfaced ramus seems to have been facilitated by the close surgical approximation of segments and the postoperative mandibular functional rehabilitation, even with segmental positional changes.

pathology