Kinetic Profile of the Transcriptome Changes Induced in the Choroid Plexus by Peripheral Inflammation

Abstract

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.

Lipocalin 2 modulates the cellular response to amyloid beta

“…CP epithelial cells from rats or mice pups were used to determine the response to Ab. CP epithelial cells were prepared as described elsewhere, 49 with minor modifications. Briefly, neonates (P5-P7) were killed and the CP dissected from the four brain ventricles, under a conventional light microscope (SZX7, Olympus, Hamburg, Germany).…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Such an approach has already been performed in adult mice [89] and rats [111]. To the best of our knowledge, the only prenatal study comparing choroid plexuses according to their localization during development was performed in a unique stage of mouse fetuses (E18.5) [85].…”

“…5c). Indeed, the choroid plexus transcriptome, proteome, and secretome are dynamic and rapidly change in response to external cues, such as inflammation [89,155]. Choroid plexus epithelial cells have many villi, providing a large surface area for detection of signals in the CSF.…”

How does bacterial endotoxin influence gonadoliberin/gonadotropins secretion and action?

“…The integrity, paracellular permeability and polarization of epithelial cells, in which the BCSFB is localized, depend on the expression of tight junction (TJ) proteins (Wolburg and Lippoldt, 2002). Studies on mice demonstrated that LPS can affect the integrity of the BCSFB by down-regulation of TJ protein expression which could alter interactions between circulating and central mediators (Marques et al, 2009a). In ewes, the amount of TJ proteins in the choroid plexus is modulated by photoperiod -higher during short than long days (Lagaraine et al, 2011), which suggests a potential photoperiodic differentiation of LPS effect on TJ protein expression in the choroid plexus of ewes.…”