Author: Romain Troubat1, Pascal Barone1, Samuel Leman1, Thomas Desmidt1,2, Arnaud Cressant1, Boriana Atanasova1, Bruno Brizard1, Wissam El Hage1,2, Alexandre Surget1, Catherine Belzung1, Vincent Camus1,2
1 UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
2 CHRU de Tours, Tours, France.
Conference/Journal: Eur J Neurosci
Date published: 2021 Jan 1
Other: Volume ID: 53 , Issue ID: 1 , Pages: 151-171 , Special Notes: doi: 10.1111/ejn.14720. , Word Count: 228
Some recent clinical and preclinical evidence suggests that neuroinflammation is a key factor that interacts with the three neurobiological correlates of major depressive disorder: depletion of brain serotonin, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and alteration of the continuous production of adult-generated neurons in the dentate gyrus of the hippocampus. This review discusses the main players in brain immunity as well as how inflammation interacts with the above three mechanisms. It is reported that kynurenine (KYN) pathway alteration in favour of its excitotoxic component and HPA axis dysregulation have the common effect of increasing extracellular glutamate levels and glutamate neurotransmission, which can impact hippocampal neurogenesis. This pathophysiological cascade appears to be triggered or sustained and reinforced by any chronic inflammatory condition involving increased circulating markers of inflammation that are able to cross the blood-brain barrier and activate microglia; it can also be the consequence of primary brain neuroinflammation, such as in neurodegenerative disorders with early manifestations that are frequently depressive symptoms. Further recent data indicate that primary microglial activation may also result from a direct impact of chronic stress on vascular function. The intricated dynamic crosstalk between neuroinflammation and other relevant neurobiological correlates of depression add to evidence that neuroinflammation may be a key therapeutic target for future therapeutic strategies in major depressive disorder.
Keywords: HPA axis; cytokines; depression; hippocampal neurogenesis; kynurenine; microglia; neuroinflammation; serotonin.
PMID: 32150310 DOI: 10.1111/ejn.14720