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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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LPS increases the expression of pro-inflammatory mediators whereas IGF-I attenuates their expression. Steady-state mRNA expression for IL-1β (A), TNFα (B), iNOS (C) and IL-6 (D) was quantified by real-time rtPCR. Expression was relative to GAPDH. *p < 0.05 following mean separation. n = 10 to 12 per treatment
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Figure 4: LPS increases the expression of pro-inflammatory mediators whereas IGF-I attenuates their expression. Steady-state mRNA expression for IL-1β (A), TNFα (B), iNOS (C) and IL-6 (D) was quantified by real-time rtPCR. Expression was relative to GAPDH. *p < 0.05 following mean separation. n = 10 to 12 per treatment

Mentions: To assess the possible inducing effect of IGF-I on neuroprotective factors, expression of IGF-I and BDNF were quantified in the brains of mice. The major IGF-I transcript in the mouse brain, IGF-IEa, was unaffected by either LPS or IGF-I (Figure 3A). In contrast, IGF-IEb was reduced by LPS [F (1,45) = 4.5, p < 0.05] (Figure 3B) but similar to IGF-IEa, IGF-IEb was not significantly changed by IGF-I. BDNF is synthesized from multiple transcripts, all of which are expressed in the brain. LPS differentially regulated BDNF transcripts. BDNF I-IX (Figure 3C) was decreased by LPS [F (1,44) = 8.8, p < 0.005], whereas BDNF VI-IX was unaffected by LPS (Figure 4D). Transcripts for both BDNF I-IX [F (1,44) = 5.2, p < 0.05] and BDNF VI-IX [F (1,45) = 5.2, p < 0.05] were elevated by IGF-I. These important results suggest that elevated BDNF expression could be one of the mechanisms underlying IGF-Is' ability to diminish depressive-like behavior of mice.


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)

LPS increases the expression of pro-inflammatory mediators whereas IGF-I attenuates their expression. Steady-state mRNA expression for IL-1β (A), TNFα (B), iNOS (C) and IL-6 (D) was quantified by real-time rtPCR. Expression was relative to GAPDH. *p < 0.05 following mean separation. 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 4: LPS increases the expression of pro-inflammatory mediators whereas IGF-I attenuates their expression. Steady-state mRNA expression for IL-1β (A), TNFα (B), iNOS (C) and IL-6 (D) was quantified by real-time rtPCR. Expression was relative to GAPDH. *p < 0.05 following mean separation. n = 10 to 12 per treatment
Mentions: To assess the possible inducing effect of IGF-I on neuroprotective factors, expression of IGF-I and BDNF were quantified in the brains of mice. The major IGF-I transcript in the mouse brain, IGF-IEa, was unaffected by either LPS or IGF-I (Figure 3A). In contrast, IGF-IEb was reduced by LPS [F (1,45) = 4.5, p < 0.05] (Figure 3B) but similar to IGF-IEa, IGF-IEb was not significantly changed by IGF-I. BDNF is synthesized from multiple transcripts, all of which are expressed in the brain. LPS differentially regulated BDNF transcripts. BDNF I-IX (Figure 3C) was decreased by LPS [F (1,44) = 8.8, p < 0.005], whereas BDNF VI-IX was unaffected by LPS (Figure 4D). Transcripts for both BDNF I-IX [F (1,44) = 5.2, p < 0.05] and BDNF VI-IX [F (1,45) = 5.2, p < 0.05] were elevated by IGF-I. These important results suggest that elevated BDNF expression could be one of the mechanisms underlying IGF-Is' ability to diminish depressive-like behavior of mice.

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