Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide

J Neuroinflammation. 2011 Dec 21;8:179. doi: 10.1186/1742-2094-8-179.

Abstract

Centrally administered insulin-like growth factor (IGF)-I has anti-depressant activity in several rodent models, including lipopolysaccharide (LPS)-induced depression. In this study we tested the ability of IGF-I and GPE (the N-terminal tri-peptide derived from IGF-I) to alter depression-like behavior induced by intraperitoneal (i.p.) administration of LPS in a preventive and curative manner. In the first case, IGF-I (1 μg) or GPE (5 μg) was administered i.c.v. to CD-1 mice followed 30 min later by 330 μg/kg body weight i.p. LPS. In the second case, 830 μg/kg body weight LPS was given 24 h prior to either IGF-I or GPE. When administered i.p., LPS induced full-blown sickness assessed as a loss of body weight, decrease in food intake and sickness behavior. None of these indices were affected by IGF-I or GPE. LPS also induced depression-like behavior; assessed as an increased duration of immobility in the tail suspension and forced swim tests. When administered before or after LPS, IGF-I and GPE abrogated the LPS response; attenuating induction of depression-like behaviors and blocking preexistent depression-like behaviors. Similar to previous work with IGF-I, GPE decreased brain expression of cytokines in response to LPS although unlike IGF-I, GPE did not induce the expression of brain-derived neurotrophic factor (BDNF). LPS induced expression of tryptophan dioxygenases, IDO1, IDO2 and TDO2, but expression of these enzymes was not altered by GPE. Thus, both IGF-I and GPE elicit specific improvement in depression-like behavior independent of sickness, an action that could be due to their anti-inflammatory properties.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Biomarkers / metabolism
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / physiology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Depression / drug therapy*
  • Eating / drug effects
  • Exploratory Behavior / drug effects
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Injections, Intraperitoneal
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor I / therapeutic use*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Motor Activity / drug effects
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Peptides / therapeutic use*

Substances

  • Biomarkers
  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Lipopolysaccharides
  • Nerve Growth Factors
  • Peptides
  • Insulin-Like Growth Factor I