Unravelling the neuroinflammatory links in depression: the potential of a lipopolysaccharide preclinical model

Abstract

Neuroinflammation has emerged as a significant contributor in the development of major depressive disorder (MDD). It has been suggested that neuroinflammation may potentially be an underlying mechanism driving several other theories in the pathogenesis of this multifactorial disorder. Despite this, the exact pathophysiology of neuroinflammation induced MDD along with the anti-inflammatory properties of both established and novel antidepressants remains unclear. Bridging this gap requires the establishment of robust preclinical models of neuroinflammation, to determine the neurobehavioral and molecular mechanisms underlying the development of depressive-like symptoms. Lipopolysaccharide (LPS), a constituent of gram-negative bacterial outer membranes, is a potent proinflammatory stimulus used as a model of various inflammatory conditions. Animal studies using LPS-induced neuroinflammation have provided valuable insights into depressive-like behaviors, the associated pathophysiological mechanisms and antidepressant drug efficacy. Therefore, this review highlights the LPS-induced neuroinflammatory model and its role in improving our understanding of neuroinflammation-induced depressive-like symptoms, and its clinical translational ability for the preclinical assessment of antidepressant treatments.