@article{ref1,
title="Novel treatment targets based on insights in the etiology of depression: Role of IL-6 trans-signaling and stress-induced elevation of glutamate and ATP",
journal="Pharmaceuticals (Basel)",
year="2019",
author="Kalkman, H.O.",
volume="12",
number="3",
pages="-",
abstract="Inflammation and psychological stress are risk factors for major depression and suicide. Both increase central glutamate levels and activate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Both factors also affect the function of the chloride transporters, Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2), and provoke interleukin-6 (IL-6) trans-signaling. This leads to measurable increases in circulating corticosteroids, catecholamines, anxiety, somatic and psychological symptoms, and a decline in cognitive functions. Recognition of the sequence of pathological events allows the prediction of novel targets for therapeutic intervention. Amongst others, these include blockade of the big-K potassium channel, blockade of the P2X4 channel, TYK2-kinase inhibition, noradrenaline α2B-receptor antagonism, nicotinic α7-receptor stimulation, and the Sgp130Fc antibody. A better understanding of downstream processes evoked by inflammation and stress also allows suggestions for tentatively better biomarkers (e.g., SERPINA3N, MARCKS, or13 C-tryptophan metabolism). © 2019 by the author. Licensee MDPI, Basel, Switzerland.<p /><p>Language: en</p>",
language="en",
issn="1424-8247",
doi="10.3390/ph12030113",
url="http://dx.doi.org/10.3390/ph12030113"
}