Limits...
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.

Show MeSH

Related in: MedlinePlus

Expression of the gene encoding ODC in the mouse brain under basal and immune-challenged conditions. These darkfield photomicrographs of nuclear emulsion–dipped sections represent the hybridization signal of ODC mRNA 24 h after a single systemic bolus of lipopolysaccharide (LPS, 1 mg/kg body weight) or the vehicle solution (Veh). Please note the widespread distribution of ODC transcript across the CNS and the robust increase in the expression levels after systemic LPS administration (right column). 3V, third ventricle; 4V, fourth ventricle; BMA, basomedial nucleus of the amygdala; CA1–3, hippocampal areas; chp, choroid plexus; CPu, caudate putamen; DG, dentate gyrus; DMH, dorsomedial nucleus hypothalamus; epd, ependymal lining cells of ventricle walls; Hb, habenula; InC, interstitial nucleus of Cajal; IPR, interpeduncular nucleus rostral; MnPO, median preoptic nucleus; MPA, medial preoptic area; Pir2, pyriform cortex (pyramidal layer); PVT, paraventricular nucleus of the thalamus; PVN, paraventricular nucleus of the hypothalamus; SCh, suprachiasmatic nucleus: SON, supraoptic nucleus; Rt, reticular nucleus; Tu, olfactory tubercle; VmPO, ventromedial preoptic nucleus; VMH, ventromedial nucleus hypothalamus. Magnification, 1.65.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172794&req=5

fig1: Expression of the gene encoding ODC in the mouse brain under basal and immune-challenged conditions. These darkfield photomicrographs of nuclear emulsion–dipped sections represent the hybridization signal of ODC mRNA 24 h after a single systemic bolus of lipopolysaccharide (LPS, 1 mg/kg body weight) or the vehicle solution (Veh). Please note the widespread distribution of ODC transcript across the CNS and the robust increase in the expression levels after systemic LPS administration (right column). 3V, third ventricle; 4V, fourth ventricle; BMA, basomedial nucleus of the amygdala; CA1–3, hippocampal areas; chp, choroid plexus; CPu, caudate putamen; DG, dentate gyrus; DMH, dorsomedial nucleus hypothalamus; epd, ependymal lining cells of ventricle walls; Hb, habenula; InC, interstitial nucleus of Cajal; IPR, interpeduncular nucleus rostral; MnPO, median preoptic nucleus; MPA, medial preoptic area; Pir2, pyriform cortex (pyramidal layer); PVT, paraventricular nucleus of the thalamus; PVN, paraventricular nucleus of the hypothalamus; SCh, suprachiasmatic nucleus: SON, supraoptic nucleus; Rt, reticular nucleus; Tu, olfactory tubercle; VmPO, ventromedial preoptic nucleus; VMH, ventromedial nucleus hypothalamus. Magnification, 1.65.

Mentions: The distribution of ODC mRNA in vehicle-treated animals is in accordance with a previous report from Kilpelainen et al. (2000). Fig. 1 depicts representative examples of the pattern of ODC gene expression in the mouse brain. Constitutive mRNA levels were found in the cortex (layers c2 to c6), ependymal cells lining the walls of lateral ventricles (epd), median preoptic nucleus (MnPO), ventromedial preoptic nucleus (VmPO), medial preoptic area (MPA), piriform cortex 2 (Pir2), and olfactory tubercle (Tu). Hippocampal CA1, CA2, CA3, and dentate gyrus (DG) exhibited strong constitutive mRNA levels, but the signal was barely detectable in the basal ganglia and thalamic area. In the latter, the hybridization signal was positive only in the habenula (Hb), paraventricular thalamic nucleus (PVT), and reticular nucleus (Rt). On the other hand, numerous nuclei and areas of the hypothalamus and amygdala contained basal ODC mRNA levels. The intensity of the message was actually quite robust in the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCh), dorsomedial hypothalamus (DMH), ventromedial hypothalamus (VMH), and supraoptic nucleus (SON). The transcript was also detected in the choroid plexus (chp), purkinje cell layer of the cerebellar cortex, and numerous nuclei and regions of the rostral and caudal medulla (Fig. 1, bottom left).


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)

Expression of the gene encoding ODC in the mouse brain under basal and immune-challenged conditions. These darkfield photomicrographs of nuclear emulsion–dipped sections represent the hybridization signal of ODC mRNA 24 h after a single systemic bolus of lipopolysaccharide (LPS, 1 mg/kg body weight) or the vehicle solution (Veh). Please note the widespread distribution of ODC transcript across the CNS and the robust increase in the expression levels after systemic LPS administration (right column). 3V, third ventricle; 4V, fourth ventricle; BMA, basomedial nucleus of the amygdala; CA1–3, hippocampal areas; chp, choroid plexus; CPu, caudate putamen; DG, dentate gyrus; DMH, dorsomedial nucleus hypothalamus; epd, ependymal lining cells of ventricle walls; Hb, habenula; InC, interstitial nucleus of Cajal; IPR, interpeduncular nucleus rostral; MnPO, median preoptic nucleus; MPA, medial preoptic area; Pir2, pyriform cortex (pyramidal layer); PVT, paraventricular nucleus of the thalamus; PVN, paraventricular nucleus of the hypothalamus; SCh, suprachiasmatic nucleus: SON, supraoptic nucleus; Rt, reticular nucleus; Tu, olfactory tubercle; VmPO, ventromedial preoptic nucleus; VMH, ventromedial nucleus hypothalamus. Magnification, 1.65.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Expression of the gene encoding ODC in the mouse brain under basal and immune-challenged conditions. These darkfield photomicrographs of nuclear emulsion–dipped sections represent the hybridization signal of ODC mRNA 24 h after a single systemic bolus of lipopolysaccharide (LPS, 1 mg/kg body weight) or the vehicle solution (Veh). Please note the widespread distribution of ODC transcript across the CNS and the robust increase in the expression levels after systemic LPS administration (right column). 3V, third ventricle; 4V, fourth ventricle; BMA, basomedial nucleus of the amygdala; CA1–3, hippocampal areas; chp, choroid plexus; CPu, caudate putamen; DG, dentate gyrus; DMH, dorsomedial nucleus hypothalamus; epd, ependymal lining cells of ventricle walls; Hb, habenula; InC, interstitial nucleus of Cajal; IPR, interpeduncular nucleus rostral; MnPO, median preoptic nucleus; MPA, medial preoptic area; Pir2, pyriform cortex (pyramidal layer); PVT, paraventricular nucleus of the thalamus; PVN, paraventricular nucleus of the hypothalamus; SCh, suprachiasmatic nucleus: SON, supraoptic nucleus; Rt, reticular nucleus; Tu, olfactory tubercle; VmPO, ventromedial preoptic nucleus; VMH, ventromedial nucleus hypothalamus. Magnification, 1.65.
Mentions: The distribution of ODC mRNA in vehicle-treated animals is in accordance with a previous report from Kilpelainen et al. (2000). Fig. 1 depicts representative examples of the pattern of ODC gene expression in the mouse brain. Constitutive mRNA levels were found in the cortex (layers c2 to c6), ependymal cells lining the walls of lateral ventricles (epd), median preoptic nucleus (MnPO), ventromedial preoptic nucleus (VmPO), medial preoptic area (MPA), piriform cortex 2 (Pir2), and olfactory tubercle (Tu). Hippocampal CA1, CA2, CA3, and dentate gyrus (DG) exhibited strong constitutive mRNA levels, but the signal was barely detectable in the basal ganglia and thalamic area. In the latter, the hybridization signal was positive only in the habenula (Hb), paraventricular thalamic nucleus (PVT), and reticular nucleus (Rt). On the other hand, numerous nuclei and areas of the hypothalamus and amygdala contained basal ODC mRNA levels. The intensity of the message was actually quite robust in the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCh), dorsomedial hypothalamus (DMH), ventromedial hypothalamus (VMH), and supraoptic nucleus (SON). The transcript was also detected in the choroid plexus (chp), purkinje cell layer of the cerebellar cortex, and numerous nuclei and regions of the rostral and caudal medulla (Fig. 1, bottom left).

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