Beta-trace Protein as a new non-invasive immunological Marker for Quinolinic Acid-induced impaired Blood-Brain Barrier Integrity

Abstract

Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity. The research hypotheses were tested in three subsamples with different states of immune activation (patients with HCV-infection and interferon-α, patients with major depression, and healthy controls). BTP has also been described as a sensitive marker in detecting impaired renal function. Thus, the renal function has been considered. Our study results revealed highest quinolinic acid and highest BTP- levels in the subsample of patients with HCV in comparison with the other subsamples with lower or no immune activation (quinolinic acid: F = 21.027, p < 0.001 [ANOVA]; BTP: F = 6.792, p < 0.01 [ANOVA]). In addition, a two-step hierarchical linear regression model showed that significant predictors of BTP levels are quinolinic acid, glomerular filtration rate and age. The neurotoxin quinolinic acid may impair blood-brain barrier integrity. BTP might be a new non-invasive biomarker to indicate quinolinic acid-induced impaired blood-brain barrier integrity.

IDO and Kynurenine Metabolites in Peripheral and CNS Disorders

“…Quite apart from the neuroimmunological activity of quinolinic acid, it can increase the permeability of the bloodbrain barrier (149)(150)(151)(152), an effect intriguingly opposed by kynurenic acid (153). Not only would this allow inflammatory mediators easier access to the CNS cells but it would also facilitate passage of leukocytes directly into the brain parenchyma.…”

Revisiting the tryptophan-serotonin deficiency and the inflammatory hypotheses of major depression in a biopsychosocial approach

“…This study is part of our research project on the ethiopathogenesis and health consequences of major depression. In former published studies ( Baranyi et al, 2015a ; Baranyi et al, 2016 ; Baranyi et al, 2017 ) of this research project we have investigated primarily the impact of beta-trace protein (BTP) as a new non-invasive immunological marker for QA-induced impaired blood-brain barrier integrity ( Baranyi et al, 2017 ). Later we have described the nitric oxide-related biological pathways ( Baranyi et al, 2015a ), and finally we have explored the impact of branched-chain amino acids (BCAAs) as new biomarkers of major depression ( Baranyi et al, 2016 ).…”

“…Blood was sampled from the fasting subjects with major depression between 08.00 and 09.00 am at the time of in-patient admittance to the Department of Psychiatry for the assays of TRP, KYN, KA and QA. The already mentioned first study ( Baranyi et al, 2017 ) of our research project of the impact of BTP as a marker for QA-induced impaired blood-brain barrier integrity consisted of a smaller data set of only 61 patients with major depression and 45 healthy controls. Thus, a part of the QA data of this enlarged present study has already been published in a completely different context, where it was evaluated for the first time whether BTP might be a new non-invasive immunological marker for QA-induced impaired blood-brain barrier integrity ( Baranyi et al, 2017 ).…”

“…Excessive microenvironment glutamate concentrations cause neurotoxicity ( Wichers & Maes, 2002 ; Wichers et al, 2005 ; Tavares et al, 2002 ). Beta-Trace Protein (BTP) might be a non-invasive biomarker to indicate QA-induced impaired blood- brain barrier integrity ( Baranyi et al, 2017 ). Another metabolite of KYN is Kynurenic Acid (KA), an antagonist of the glutamate recognition site of the NMDA receptor.…”

Breakdown of the Paracellular Tight and Adherens Junctions in the Gut and Blood Brain Barrier and Damage to the Vascular Barrier in Patients with Deficit Schizophrenia<strong></strong>

“…Furthermore, inflammation may disrupt the TJs thereby promoting paracellular opening of the BBB (Stolp and Dziegielewska, 2009;Varatharaj and Galea, 2017). Some neurotoxic TRYCATS such as quinolinic acid may also impair BBB integrity (Baranyi et al, 2017), while CCL-11 downregulates TJ proteins (occludin, zona occludens-1 and claudin-1) in a concentration-dependent manner in human coronary artery endothelial cells (Jamaluddin et al, 2009). In addition, CCL-11 is rapidly transported from the blood to brain with a slow phase of influx preceding a rapid phase and consequently CCL-11 accumulates in many brain regions (Erickson et al, 2014).…”