Limits...
Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors.

Lawson MA, Parrott JM, McCusker RH, Dantzer R, Kelley KW, O'Connor JC - J Neuroinflammation (2013)

Bottom Line: LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution.These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine.Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Activation of the tryptophan degrading enzyme indoleamine-2,3-dioxygenase 1 (IDO1) is associated with the development of behavioral signs of depression. Systemic immune challenge induces IDO1 in both the periphery and the brain, leading to increased circulating and brain concentrations of kynurenines. However, whether IDO1 activity within the brain is necessary for the manifestation of depression-like behavior of mice following a central immune challenge remains to be elucidated.

Methods: We investigated the role of brain IDO1 in mediating depression-like behavior of mice in response to intracerebroventricular injection of saline or lipopolysaccharide (LPS, 10 ng).

Results: LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution. These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine. Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test.

Conclusions: These data indicate that activation of brain IDO1 is sufficient to induce depression-like behaviors of mice in response to central LPS.

Show MeSH

Related in: MedlinePlus

Lipopolysaccharide administered via intracerebroventricular injection induced body weight loss and depression-like behavior. (a) Lipopolysaccharide (LPS; 10 ng) decreased body weight over a 24-hour period following treatment. (b) Sucrose preference was decreased by intracerebroventricular LPS. (c) LPS increased tail suspension test (TST) immobility. Data are the average ± standard error of the mean. *P <0.05, **P <0.01. n = 7 mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3733827&req=5

Figure 1: Lipopolysaccharide administered via intracerebroventricular injection induced body weight loss and depression-like behavior. (a) Lipopolysaccharide (LPS; 10 ng) decreased body weight over a 24-hour period following treatment. (b) Sucrose preference was decreased by intracerebroventricular LPS. (c) LPS increased tail suspension test (TST) immobility. Data are the average ± standard error of the mean. *P <0.05, **P <0.01. n = 7 mice per group.

Mentions: To confirm that central LPS induced a sickness response, we measured the change in body weight. As expected, Balb/c mice injected ICV with 10 ng LPS lost body weight over a 24-hour period following treatment (F1,12 = 5.63, P <0.05; Figure 1a). We further evaluated whether central LPS induced depression-like behaviors. Sucrose preference was measured during the 24-hour period following treatment. LPS-treated mice displayed a significant decrease in sucrose preference (F1,12 = 8.31, P <0.05; Figure 1b). Mice were then submitted to the TST 24 hours after treatment. LPS caused a significant increase in the duration of immobility when compared with saline-treated control mice (F1,12 = 16.18, P <0.01; Figure 1c).


Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors.

Lawson MA, Parrott JM, McCusker RH, Dantzer R, Kelley KW, O'Connor JC - J Neuroinflammation (2013)

Lipopolysaccharide administered via intracerebroventricular injection induced body weight loss and depression-like behavior. (a) Lipopolysaccharide (LPS; 10 ng) decreased body weight over a 24-hour period following treatment. (b) Sucrose preference was decreased by intracerebroventricular LPS. (c) LPS increased tail suspension test (TST) immobility. Data are the average ± standard error of the mean. *P <0.05, **P <0.01. n = 7 mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3733827&req=5

Figure 1: Lipopolysaccharide administered via intracerebroventricular injection induced body weight loss and depression-like behavior. (a) Lipopolysaccharide (LPS; 10 ng) decreased body weight over a 24-hour period following treatment. (b) Sucrose preference was decreased by intracerebroventricular LPS. (c) LPS increased tail suspension test (TST) immobility. Data are the average ± standard error of the mean. *P <0.05, **P <0.01. n = 7 mice per group.
Mentions: To confirm that central LPS induced a sickness response, we measured the change in body weight. As expected, Balb/c mice injected ICV with 10 ng LPS lost body weight over a 24-hour period following treatment (F1,12 = 5.63, P <0.05; Figure 1a). We further evaluated whether central LPS induced depression-like behaviors. Sucrose preference was measured during the 24-hour period following treatment. LPS-treated mice displayed a significant decrease in sucrose preference (F1,12 = 8.31, P <0.05; Figure 1b). Mice were then submitted to the TST 24 hours after treatment. LPS caused a significant increase in the duration of immobility when compared with saline-treated control mice (F1,12 = 16.18, P <0.01; Figure 1c).

Bottom Line: LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution.These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine.Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Activation of the tryptophan degrading enzyme indoleamine-2,3-dioxygenase 1 (IDO1) is associated with the development of behavioral signs of depression. Systemic immune challenge induces IDO1 in both the periphery and the brain, leading to increased circulating and brain concentrations of kynurenines. However, whether IDO1 activity within the brain is necessary for the manifestation of depression-like behavior of mice following a central immune challenge remains to be elucidated.

Methods: We investigated the role of brain IDO1 in mediating depression-like behavior of mice in response to intracerebroventricular injection of saline or lipopolysaccharide (LPS, 10 ng).

Results: LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution. These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine. Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test.

Conclusions: These data indicate that activation of brain IDO1 is sufficient to induce depression-like behaviors of mice in response to central LPS.

Show MeSH
Related in: MedlinePlus