Paricalcitol alleviates lipopolysaccharide-induced depressive-like behavior by suppressing hypothalamic microglia activation and neuroinflammation

Biochem Pharmacol. 2019 May;163:1-8. doi: 10.1016/j.bcp.2019.01.021. Epub 2019 Jan 28.

Abstract

Depression is highly prevalent in patients suffering from chronic inflammatory diseases. Dysregulated neuroinflammation and concomitant activated microglia play a pivotal role in the pathogenesis of depression. Paricalcitol (Pari), a vitamin D2 analogue, has been demonstrated to exert anti-inflammative effects on renal and cardiovascular diseases. In this study, mice were pretreated with Pari before being induced to acute depression-like behaviors by systemic lipopolysaccharide (LPS) injection. To determine the therapeutic effects of Pari, alterations in acute body weight, sucrose preference, forced swimming and tail suspension tests were assessed. Then, alterations of pro-inflammation cytokine IL1-β level and microglia activity in the hypothalamus, which are involved in the pathophysiology of depression, were examined. The results showed that Pari significantly alleviated systemic LPS injection induced depressive-like behaviors as shown by increased sucrose preference and decreased TST and FST immobility. Pari could specifically regulate microglia-mediated neuroinflammation process and local activity of renin-angiotensin system to exert its anti-depressant effects. This study demonstrated a potential for paricalcitol in treating depressive symptoms induced by systemic inflammation, particularly in patients with chronic hypertension.

Keywords: Depression-like behavior; LPS; Microgliosis; Neuroinflammation; Paricalcitol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Depression / chemically induced
  • Depression / drug therapy*
  • Depression / metabolism
  • Ergocalciferols / pharmacology
  • Ergocalciferols / therapeutic use*
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / metabolism

Substances

  • Antidepressive Agents
  • Ergocalciferols
  • Inflammation Mediators
  • Lipopolysaccharides
  • paricalcitol