Analysis of the Effects of Sex Hormone Background on the Rat Choroid Plexus Transcriptome by cDNA Microarrays

Abstract

The choroid plexus (CP) are highly vascularized branched structures that protrude into the ventricles of the brain, and form a unique interface between the blood and the cerebrospinal fluid (CSF), the blood-CSF barrier, that are the main site of production and secretion of CSF. Sex hormones are widely recognized as neuroprotective agents against several neurodegenerative diseases, and the presence of sex hormones cognate receptors suggest that it may be a target for these hormones. In an effort to provide further insight into the neuroprotective mechanisms triggered by sex hormones we analyzed gene expression differences in the CP of female and male rats subjected to gonadectomy, using microarray technology. In gonadectomized female and male animals, 3045 genes were differentially expressed by 1.5-fold change, compared to sham controls. Analysis of the CP transcriptome showed that the top-five pathways significantly regulated by the sex hormone background are olfactory transduction, taste transduction, metabolism, steroid hormone biosynthesis and circadian rhythm pathways. These results represent the first overview of global expression changes in CP of female and male rats induced by gonadectomy and suggest that sex hormones are implicated in pathways with central roles in CP functions and CSF homeostasis.

‘Smelling’ the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus

“…It is interesting to note that 5 of the 11 identified ORs were cloned multiple times, suggesting more abundant species. With the exception of Olr1082, all the OR transcripts had been previously detected in our recent microarray study [18]. We also used an OR antibody (OR19) in IHC, whose transcripts were detected in the microarray analysis and confirmed in the present study by RT-PCR, and positive staining was obtained in the epithelial cells of rat CP slices.…”

“…We also used an OR antibody (OR19) in IHC, whose transcripts were detected in the microarray analysis and confirmed in the present study by RT-PCR, and positive staining was obtained in the epithelial cells of rat CP slices. As reported in the cDNA microarray study [18], hormone decline in rat CP had effects in olfactory transduction signaling, with several genes being up-or down-regulated, in both sexes. Among these genes regulated by sex hormones, most are ORs and the Olr19 is included in the upregulated gene list (female ovariectomized rats vs sham rats).…”

“…However, in our previous study on the rat CP trancriptome [18], we detected all the AC isoforms (AC1 to AC10), with different levels of expression.…”

“…The presence of olfactory signaling transcripts in the rat CP has been previously demonstrated in a cDNA microarray study aiming to compare the effect of sex hormones on the CP transcriptome [18]. A detailed analysis of the olfactory-related list of genes showed a significant number of genes regulated by sex hormones, most of them corresponding to ORs (95-99%; data not shown).…”

“…Our previous studies on the effects of the sex hormone background in rat CP transcriptome have revealed differential expression of a group of olfactory transduction pathway genes [18]; most of them are ORs. This was the first report describing the presence of olfactory signaling transcripts in the CP.…”