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Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system.

Soulet D, Rivest S - J. Cell Biol. (2003)

Bottom Line: This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells.In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion.Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Endocrinology, CHUL Research Center, Laval University, Quebec, Canada G1V 4G2.

ABSTRACT
The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.

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Related in: MedlinePlus

Confocal laser scanning microscopic image of ODC-immunoreactive (ir) signal within neurons and microglia in the cerebral cortex. Neuronal nuclei were labeled by means of a primary antibody directed against NeuN and a secondary antibody conjugated to Alexa Fluor® 546 (A and E, blue nuclei). The secondary antibody used to label ODC was coupled to Cy2 (B and F, green), whereas a Cy5 secondary antibody was used to bind the primary antibody directed against ionized calcium binding adaptor molecule 1 (C and G, iba1) expressed within cells of myeloid lineage (red). D is an overlay of A–C. H is an overlay of E–G. White arrows show double-labeled neurons (ODC-ir/NeuN-ir), whereas white arrowheads show double-labeled microglial cells (ODC-ir/iba1-ir).
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fig2: Confocal laser scanning microscopic image of ODC-immunoreactive (ir) signal within neurons and microglia in the cerebral cortex. Neuronal nuclei were labeled by means of a primary antibody directed against NeuN and a secondary antibody conjugated to Alexa Fluor® 546 (A and E, blue nuclei). The secondary antibody used to label ODC was coupled to Cy2 (B and F, green), whereas a Cy5 secondary antibody was used to bind the primary antibody directed against ionized calcium binding adaptor molecule 1 (C and G, iba1) expressed within cells of myeloid lineage (red). D is an overlay of A–C. H is an overlay of E–G. White arrows show double-labeled neurons (ODC-ir/NeuN-ir), whereas white arrowheads show double-labeled microglial cells (ODC-ir/iba1-ir).

Mentions: To ascertain the cellular localization of ODC in the untreated mouse brain, a multiple labeling approach was performed. As depicted by Fig. 2, the positive signal in both neuronal and microglial cells was confirmed via triple immunohistochemistry labeling and confocal laser scanning microscopy. Cytoplasmic ODC protein (Fig. 2, green) colocalized with the specific marker of neuronal nuclei NeuN (Fig. 2, blue), which provides the anatomical evidence that neurons have the ability to produce polyamines. ODC-immunoreactive cells also colocalized with a marker of microglial cells, iba1. (Fig. 2, red). However, ODC+/NeuN+ cells were clearly more numerous and widely distributed than ODC+/iba1+ cells across the cerebral tissue of mice injected systemically with the bacterial cell wall component.


Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system.

Soulet D, Rivest S - J. Cell Biol. (2003)

Confocal laser scanning microscopic image of ODC-immunoreactive (ir) signal within neurons and microglia in the cerebral cortex. Neuronal nuclei were labeled by means of a primary antibody directed against NeuN and a secondary antibody conjugated to Alexa Fluor® 546 (A and E, blue nuclei). The secondary antibody used to label ODC was coupled to Cy2 (B and F, green), whereas a Cy5 secondary antibody was used to bind the primary antibody directed against ionized calcium binding adaptor molecule 1 (C and G, iba1) expressed within cells of myeloid lineage (red). D is an overlay of A–C. H is an overlay of E–G. White arrows show double-labeled neurons (ODC-ir/NeuN-ir), whereas white arrowheads show double-labeled microglial cells (ODC-ir/iba1-ir).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172794&req=5

fig2: Confocal laser scanning microscopic image of ODC-immunoreactive (ir) signal within neurons and microglia in the cerebral cortex. Neuronal nuclei were labeled by means of a primary antibody directed against NeuN and a secondary antibody conjugated to Alexa Fluor® 546 (A and E, blue nuclei). The secondary antibody used to label ODC was coupled to Cy2 (B and F, green), whereas a Cy5 secondary antibody was used to bind the primary antibody directed against ionized calcium binding adaptor molecule 1 (C and G, iba1) expressed within cells of myeloid lineage (red). D is an overlay of A–C. H is an overlay of E–G. White arrows show double-labeled neurons (ODC-ir/NeuN-ir), whereas white arrowheads show double-labeled microglial cells (ODC-ir/iba1-ir).
Mentions: To ascertain the cellular localization of ODC in the untreated mouse brain, a multiple labeling approach was performed. As depicted by Fig. 2, the positive signal in both neuronal and microglial cells was confirmed via triple immunohistochemistry labeling and confocal laser scanning microscopy. Cytoplasmic ODC protein (Fig. 2, green) colocalized with the specific marker of neuronal nuclei NeuN (Fig. 2, blue), which provides the anatomical evidence that neurons have the ability to produce polyamines. ODC-immunoreactive cells also colocalized with a marker of microglial cells, iba1. (Fig. 2, red). However, ODC+/NeuN+ cells were clearly more numerous and widely distributed than ODC+/iba1+ cells across the cerebral tissue of mice injected systemically with the bacterial cell wall component.

Bottom Line: This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells.In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion.Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Endocrinology, CHUL Research Center, Laval University, Quebec, Canada G1V 4G2.

ABSTRACT
The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.

Show MeSH
Related in: MedlinePlus