The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

Yong Ku Kim, Kyoung Sae Na, Aye Mu Myint, Brian E. Leonard

Research output: Contribution to journalArticlepeer-review

219 Citations (Scopus)

Abstract

Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GRs) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the anti-oxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GRs have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume64
DOIs
Publication statusPublished - 2016 Jan 4

Keywords

  • Antioxidants
  • Cytokine
  • Depression
  • Glucocorticoid receptor
  • Neuroinflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression'. Together they form a unique fingerprint.

Cite this