Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression

Physiol Behav. 2016 Jul 1;161:166-173. doi: 10.1016/j.physbeh.2016.04.034. Epub 2016 Apr 19.


Our previous work found that triple central lipopolysaccharide (LPS) administration could induce depressive-like behaviors and increased central pro-inflammatory cytokines mRNA, hippocampal cytokine mRNA in particular. Since several neuroinflammation-associated conditions have been reported to impair neurogenesis, in this study, we further investigated whether the neuroinflammation induced depression would be associated with hippocampal neurogenesis dysfunction. An animal model of depression induced by triple central lipopolysaccharide (LPS) administration was used. In the hippocampus, the neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α. It was found that rats in the neuroinflammatory state exhibited depressive-like behaviors, including reduced saccharin preference and locomotor activity as well as increased immobility time in the tail suspension test and latency to feed in the novelty suppressed feeding test. Adult hippocampal neurogenesis was concomitantly inhibited, including decreased cell proliferation and newborn cell survival. We also demonstrated that the decreased hippocampal neurogenesis in cell proliferation was significantly correlated with the depressive-like phenotypes of decreased saccharine preference and distance travelled, the core and characteristic symptoms of depression, under neuro inflammation state. These findings provide the first evidence that hippocampal neurogenesis dysfunction is correlated with neuroinflammation-induced depression, which suggests that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neruoinflammation.

Keywords: Depressive-like behavior; Lipopolysaccharide; Neurogenesis; Neuroinflammation; Pro-inflammatory cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation / drug effects
  • Cytokines / metabolism*
  • Depression / complications*
  • Disease Models, Animal
  • Encephalitis / etiology*
  • Encephalitis / pathology*
  • Exploratory Behavior / drug effects
  • Food Preferences / drug effects
  • Hindlimb Suspension
  • Hippocampus / pathology*
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / toxicity
  • Male
  • Neurogenesis / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Saccharin / administration & dosage
  • Time Factors


  • Cytokines
  • Interleukin-1beta
  • Lipopolysaccharides
  • Saccharin
  • Bromodeoxyuridine