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

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.

Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour

“…were measured. This protocol has been adapted from several previously published protocols [26][27][28]. Preference was calculated as: saccharin preference % = [saccharin cons./(saccharin cons.…”

The impact of prenatal stress on insulin-like growth factor-1 and pro-inflammatory cytokine expression in the brains of adult male rats: The possible role of suppressors of cytokine signaling proteins

“…Deficits in both central and peripheral IGF-1 levels may contribute to the development of affective disorders in humans and lead to the progression of depression-like symptoms in animals (Mitschelen et al, 2011). Furthermore, IGF-1 displays antidepressant-like properties: intracerebroventricular administration of IGF-1 reverses lipopolysaccharide (LPS)-evoked depression-like behavior in rodents (Park et al, 2011). It has been shown that lipopolysaccharide (LPS)-a nonspecific immune response activator-administered intraperitoneally causes alterations in cytokine levels and leads to behavioral disturbances known as "sickness behavior".…”

Immune–neural connections: how the immune system’s response to infectious agents influences behavior

“…TNF within the brain can derive from peripheral expression, expression within the brain dependent on neural input (Marquette et al, 2003), secretion within the brain in response to humoral stimuli by PAMPs or cytokines (Bluthé et al, 2002;Churchill et al, 2006;Park et al, 2011b) or exogenous addition to the brain (Bluthé et al, 2006). Current dogma suggests that all sources have the same behavioral effect: TNF induces sickness behavior, reminiscent of the actions of IL-1.…”

“…) or peripheral (i.p.) LPS induces a depressive-like phenotype when quantified as increased time of immobility in the TST and FST (Park et al, 2011a;Park et al, 2011b). The increased time of immobility in these tests is frequently used as an index of despair.…”

“…In contrast, a higher dosage of LPS is required when administered i.p. (Park et al, 2011b). At 330 or 830gkg -1 body mass i.p.…”