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Kalkman HO. 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. Pharmaceuticals (Basel). 2019;12(3)doi: 10.3390/ph12030113.
Kalkman, H. O. (2019). 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. Pharmaceuticals (Basel, Switzerland), 12(3), . https://doi.org/10.3390/ph12030113
Kalkman, Hans O. "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." Pharmaceuticals (Basel, Switzerland) vol. 12,3 (2019). doi: https://doi.org/10.3390/ph12030113
Kalkman HO. 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. Pharmaceuticals (Basel). 2019 Jul 29;12(3). doi: 10.3390/ph12030113. PMID: 31362361; PMCID: PMC6789839.
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Pharmaceuticals (Basel). 2019 Jul 29;12(3). doi: 10.3390/ph12030113.

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.

Pharmaceuticals (Basel, Switzerland)

Hans O Kalkman

Affiliations

  1. Retired pharmacologist, Gänsbühlgartenweg 7, CH4132 Muttenz, Switzerland. [email protected].

PMID: 31362361 PMCID: PMC6789839 DOI: 10.3390/ph12030113

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, or

Keywords: inflammasome; ketamine; major depressive disorder; suicide; vagus nerve

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