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Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice.

Park SE, Dantzer R, Kelley KW, McCusker RH - J Neuroinflammation (2011)

Bottom Line: Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS.LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP).These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Integrated Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801-3873, USA.

ABSTRACT
Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.

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IGF-I displays anti-depressant activity in the presence or absence of LPS. IGF-I (1000 ng) or (PBS) was administered i.c.v. 30 min before i.c.v. PBS or LPS (10 ng). Depressive-like behavior was assessed as immobility in the TST to define the effect of IGF-I (A), fluoxetine and desipramine (B) on depressive-like behavior. n = 16 to 19 per treatment for data in (A) and n = 8 for 9 for the data in (B)
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Figure 1: IGF-I displays anti-depressant activity in the presence or absence of LPS. IGF-I (1000 ng) or (PBS) was administered i.c.v. 30 min before i.c.v. PBS or LPS (10 ng). Depressive-like behavior was assessed as immobility in the TST to define the effect of IGF-I (A), fluoxetine and desipramine (B) on depressive-like behavior. n = 16 to 19 per treatment for data in (A) and n = 8 for 9 for the data in (B)

Mentions: The TST was performed 9 h post LPS (Figure 1A) using mice treated i.c.v. with PBS or IGF-I (1,000 ng) 30 min prior to PBS or LPS (10 ng). As expected, LPS-treated mice exhibited an increase in immobility compared to the control groups [F (1,65) = 4.2, p < 0.05]. IGF-I significantly decreased the duration of immobility [F (1,65) = 13.1, p < 0.001]. There was no significant interaction. These data indicate that IGF-I attenuated depressive-like behavior in the absence and presence of LPS. The increased immobility that occurs 9 h after LPS administration was inhibited by fluoxetine, a classic selective serotonin reuptake inhibitor (SSRI) anti-depressant, and desipramine, a classic tricyclic anti-depressant, (Figure 1B, p < 0.05 for the main effect of LPS, p < 0.05 for the main effect of antidepressants) supporting this behavioral change after LPS as a depressive-like response. The anti-depressant effect of desipramine mimicked that of IGF-I (suppressing immobility in the absence or presence of LPS), whereas, fluoxetine did not affect immobility in control mice. Collectively, these data establish that central LPS is capable of inducing depressive-like behavior, similar to the established effect of peripheral LPS. More important, the results show that IGF-I shares with classic anti-depressants, the ability to inhibit depressive-like behavior.


Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice.

Park SE, Dantzer R, Kelley KW, McCusker RH - J Neuroinflammation (2011)

IGF-I displays anti-depressant activity in the presence or absence of LPS. IGF-I (1000 ng) or (PBS) was administered i.c.v. 30 min before i.c.v. PBS or LPS (10 ng). Depressive-like behavior was assessed as immobility in the TST to define the effect of IGF-I (A), fluoxetine and desipramine (B) on depressive-like behavior. n = 16 to 19 per treatment for data in (A) and n = 8 for 9 for the data in (B)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045937&req=5

Figure 1: IGF-I displays anti-depressant activity in the presence or absence of LPS. IGF-I (1000 ng) or (PBS) was administered i.c.v. 30 min before i.c.v. PBS or LPS (10 ng). Depressive-like behavior was assessed as immobility in the TST to define the effect of IGF-I (A), fluoxetine and desipramine (B) on depressive-like behavior. n = 16 to 19 per treatment for data in (A) and n = 8 for 9 for the data in (B)
Mentions: The TST was performed 9 h post LPS (Figure 1A) using mice treated i.c.v. with PBS or IGF-I (1,000 ng) 30 min prior to PBS or LPS (10 ng). As expected, LPS-treated mice exhibited an increase in immobility compared to the control groups [F (1,65) = 4.2, p < 0.05]. IGF-I significantly decreased the duration of immobility [F (1,65) = 13.1, p < 0.001]. There was no significant interaction. These data indicate that IGF-I attenuated depressive-like behavior in the absence and presence of LPS. The increased immobility that occurs 9 h after LPS administration was inhibited by fluoxetine, a classic selective serotonin reuptake inhibitor (SSRI) anti-depressant, and desipramine, a classic tricyclic anti-depressant, (Figure 1B, p < 0.05 for the main effect of LPS, p < 0.05 for the main effect of antidepressants) supporting this behavioral change after LPS as a depressive-like response. The anti-depressant effect of desipramine mimicked that of IGF-I (suppressing immobility in the absence or presence of LPS), whereas, fluoxetine did not affect immobility in control mice. Collectively, these data establish that central LPS is capable of inducing depressive-like behavior, similar to the established effect of peripheral LPS. More important, the results show that IGF-I shares with classic anti-depressants, the ability to inhibit depressive-like behavior.

Bottom Line: Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS.LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP).These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Integrated Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801-3873, USA.

ABSTRACT
Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.

Show MeSH
Related in: MedlinePlus