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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 decreases the expression of GFAP but not COX2. Steady-state mRNA expression for GFAP (A) and COX2 (B) were quantified by real-time rtPCR. Expression was relative to GAPDH, which was used as a housekeeping control gene. n = 10 to 12 per treatment
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Figure 6: IGF-I decreases the expression of GFAP but not COX2. Steady-state mRNA expression for GFAP (A) and COX2 (B) were quantified by real-time rtPCR. Expression was relative to GAPDH, which was used as a housekeeping control gene. n = 10 to 12 per treatment

Mentions: Glial fibrillary acidic protein (GFAP) expression was quantified to determine if IGF-I influenced astroglial activation. As shown in Figure 6, LPS did not alter expression of GFAP at 9 h. However, central treatment with IGF-I significantly decreased the expression of GFAP [F (1,44) = 4.3, p < 0.05]. As expected, LPS increased COX2 expression [F (1,44) = 7.6, p < 0.01], but this increase was not modulated by IGF-I.


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 decreases the expression of GFAP but not COX2. Steady-state mRNA expression for GFAP (A) and COX2 (B) were quantified by real-time rtPCR. Expression was relative to GAPDH, which was used as a housekeeping control gene. n = 10 to 12 per treatment
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: IGF-I decreases the expression of GFAP but not COX2. Steady-state mRNA expression for GFAP (A) and COX2 (B) were quantified by real-time rtPCR. Expression was relative to GAPDH, which was used as a housekeeping control gene. n = 10 to 12 per treatment
Mentions: Glial fibrillary acidic protein (GFAP) expression was quantified to determine if IGF-I influenced astroglial activation. As shown in Figure 6, LPS did not alter expression of GFAP at 9 h. However, central treatment with IGF-I significantly decreased the expression of GFAP [F (1,44) = 4.3, p < 0.05]. As expected, LPS increased COX2 expression [F (1,44) = 7.6, p < 0.01], but this increase was not modulated by IGF-I.

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