Kinetic profile of the transcriptome changes induced in the choroid plexus by peripheral inflammation.
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.
Marques
Fernanda
F
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, Braga, Portugal.
Sousa
João C
JC
Coppola
Giovanni
G
Falcao
Ana M
AM
Rodrigues
Ana João
AJ
Geschwind
Daniel H
DH
Sousa
Nuno
N
Correia-Neves
Margarida
M
Palha
Joana A
JA
D000210:Acute-Phase Reaction / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D007700:Kinetics; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D008070:Lipopolysaccharides