Kinetic profile of the transcriptome changes induced in the choroid plexus by peripheral inflammation

• Published in: Journal of cerebral blood flow and metabolism Vol. 29; no. 5; pp. 921 - 932
• Main Authors: Marques, Fernanda, Sousa, João Carlos, Coppola, Giovanni, Falcão, Ana Luisa Mendanha, Rodrigues, Ana João, Geschwind, Daniel H., Sousa, Nuno, Correia-Neves, M, Palha, Joana Almeida
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2009; Nature Publishing Group; Sage Publications Ltd
• Subjects: Acute-Phase Reaction - cerebrospinal fluid; Acute-Phase Reaction - chemically induced; Acute-Phase Reaction - immunology; Acute-Phase Reaction - metabolism; Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - immunology; Blood-Brain Barrier - metabolism; Cells; Cells, Cultured; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrospinal Fluid; Cerebrospinal Fluid - immunology; Cerebrospinal Fluid - metabolism; Choroid Plexus; Choroid Plexus - drug effects; Choroid Plexus - immunology; Choroid Plexus - metabolism; Cultured; Down-Regulation; Epithelial Cells; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression - drug effects; Gene Expression Profiling; Inbred C57BL; Inflammation; Kinetics; lipopolysaccharide; Lipopolysaccharides; Male; Medical sciences; Mice; Mice, Inbred C57BL; Neurology; Oligonucleotide Array Sequence Analysis; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Science & Technology; Transcriptome; Up-Regulation; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Wistar; blood-brain barrier; lipopolysaccharide; inflammation; transcriptome; cerebrospinal fluid; choroid plexus; Nervous system diseases; Central nervous system disease; Lipopolysaccharide; Choroid; Inflammation; Cerebrospinal fluid; Blood brain barrier; Cerebrovascular disease; Cerebral disorder
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.15

The choroid plexus, being part of the blood-brain barriers and responsible for the production of cerebrospinal fluid, is ideally positioned to transmit signals into and out of the brain. This study, using microarray analysis, shows that the mouse choroid plexus displays an acute-phase response after an inflammatory stimulus induced in the periphery by lipopolysaccharide (LPS). Remarkably, the response is specific to a restricted number of genes (out of a total of 24,000 genes analyzed, 252 are up-regulated and 173 are down-regulated) and transient, as it returns to basal conditions within 72 h. The up-regulated genes cluster into families implicated in immune-mediated cascades and in extracellular matrix remodeling, whereas those down-regulated participate in maintenance of the barrier function. Importantly, several acute-phase proteins, whose blood concentrations rise in response to inflammation, may contribute to the effects observed in vivo after LPS injection, as suggested by the differential response of primary choroid plexus epithelial cell cultures to LPS alone or to serum collected from animals exposed to LPS. By modulating the composition of the cerebrospinal fluid, which will ultimately influence the brain parenchyma, the choroid plexus response to inflammation may be of relevance in brain homeostasis in health and disease. This work was supported by grant POCTI/SAU-NEU/ 56618/2004 from the Portuguese Foundation for Science and Technology (FCT) /FEDER; and from a grant from the DANA foundation; Marques F, Falcao AM, and Rodrigues AJ are recipients of fellowships from FCT/FEDER.