The choroid plexus response to peripheral inflammatory signals
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1
School of Health Sciences, University of Minho, Life and Health Sciences Research Institute, Portugal
The influence of peripheral inflammation in brain status is a subject of increasing interest. The blood-choroid plexus-cerebrospinal fluid barrier functions as an interface between the periphery and the central nervous system (CNS), thus modulating the effects of peripheral inflammation in the brain. Particularly interesting is the fact that the choroid plexus secretome influences the composition of the cerebrospinal fluid which, in turn, may have consequences to various cells in the brain parenchyma. In addition, by altering the integrity of the barrier, and/or by modulating the expression levels of receptors and transporters in the epithelial cells, peripheral stimuli are likely to be transmitted into the CNS. We will address how the choroid plexus responds to peripheral inflammatory stimulus elicited by the administration of the bacterial lipopolysacharide (LPS) in mice. It is noticeable that the choroid plexus displays a rapid and transient response to an acute peripheral inflammatory stimulus, with most altered gene expression occurring at 3 to 12 hours after the LPS injection, and returning to basal levels after 72 hours. The genes found up-regulated are mostly implicated in immune-mediated cascades while those down-regulated encode for proteins involved in the maintenance of the barrier function of the CP. In vitro studies using primary choroid plexus cell cultures further revealed that LPS alone, but also cytokines whose expression increases in the blood in response to peripheral inflammation, contribute to the response elicited at the choroid plexus. Of relevance, IL6 seems to mediate the de novo expression of hepcidin, the principal regulator of systemic iron homeostasis, in response to peripheral inflammation. In addition, other iron-related proteins, such as lipocalin 2, a chelator for bacteria iron-loaded siderophores, are secreted into the cerebrospinal fluid in such conditions. These observations highlight a novel function for the choroid plexus in brain iron homeostasis, that might be of relevance not only when considering restriction of bacteria access into the brain, but also when considering iron overload in CNS disorders such as Alzheimer’s disease.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium 6 – Barriers of the Brain
Citation:
Palha
J
(2009). The choroid plexus response to peripheral inflammatory signals.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.022
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Received:
05 Aug 2009;
Published Online:
05 Aug 2009.
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Correspondence:
Joana Palha, School of Health Sciences, University of Minho, Life and Health Sciences Research Institute, Braga, Portugal, japalha@med.uminho.pt