Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain.

Abstract

Glutathione-independent prostaglandin D synthase [prostaglandin-H2 D-isomerase; (5Z,13E)-(15S)-9a,lla-epidioxy-15-hydroxyprosta-5,13-dienoate D-isomerase, EC 5.3.99.2] is an enzyme responsible for biosynthesis of prostaglandin D2 in the central nervous system. In situ hybridization with antisense RNA for the enzyme indicated that mRNA for the enzyme was predominantly expressed in the leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain. (2) is responsible for biosynthesis of PGD2 in the central nervous system (3), retina (4), and cochlea (5). Immunocytochemical studies with a polyclonal and two monoclonal anti-rat brain PGD synthase antibodies revealed that the major cellular location of the enzyme in the brain shifts postnatally from neurons of 1-to 2-week-old rats to oligodendrocytes in adult animals (6), suggesting that the enzyme may have distinct functions in those cells at each specific developmental stage and thus plays important roles in both maturation and maintenance of the central nervous system.We previously isolated cDNAs encoding this enzyme in the brain of rats (7) and humans (8). The homology search in data bases of protein primary structure (8-10) indicated that the enzyme is a member ofthe lipocalin superfamily consisting of a variety of secretory proteins involved in the transport of small hydrophobic molecules (11). PGD synthase is the only lipocalin known to be associated with enzyme activity. The gene structure of rat brain PGD synthase (12) is also remarkably conserved among the members of this protein family inThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.terms of the numbers and sizes of exons and phases and sites of exon/intron splicing.Inorganic quadrivalent selenocompounds, such as SeCL4 and Na2SeO3, have recently been found to inhibit rat brain PGD synthase activity without affecting the activities ofother enzymes in the arachidonate cascade (13). Those selenocompounds were subsequently shown to inhibit sleep in unrestrained rats, promoting physiological wakefulness, in a timeand dose-dependent manner, when administered into the third ventricle via a microdialysis probe (14). These results further support our hypothesis that PGD2 is involved in the promotion of sleep under physiological conditions and imply that the PGD synthase may be a key enzyme in regulation of sleep-wake activities.We report here, by using in situ hybridization with antisense RNA for the enzyme, that mRNA for glutathioneindependent PGD synthase is dominantly expressed in the leptomeninges and choroid plexus, as well as in oligodendrocytes, of the adult rat brain. These tissues and cells were also found to be enriched in both the immunoreactivity and the enzyme activity of PGD synthase, indicating that the major site of synthesis of the enzyme, and also of PGD2, is predominantly, if not exclusively, located in the leptomen...

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

“…Herein, we identified the prostaglandin D2 synthase (PGDS) gene as a specific marker of arachnoidal cells of rats, mice and human beings (Urade et al, 1993;Yamashima et al, 1997;Kawashima et al, 2001). We leveraged this marker to develop a new transgenic Cre strain to target Nf2 inactivation to PGDS-expressing cells and showed that they are the meningioma cell of origin capable of giving rise to both fibroblastic and meningothelial histological subtypes.…”

Dominant Expression of Rat Prostanoid DP Receptor mRNA in Leptomeninges, Inner Segments of Photoreceptor Cells, Iris Epithelium, and Ciliary Processes

“…The enzyme responsible for PGD2 synthesis in the brain, lipocalin-type PGD synthase, is expressed in the leptomeninges (Urade et al, 1993;Beuckmann et al, 1997), similar to the DP receptor. Although the enzyme was also highly expressed in choroid plexus and oligodendrocytes of the brain (Urade eta!., 1993), DP receptor mRNA was not detected in these tissues and cells, as examined by RT-PCR and in situ hybridization analyses (data not shown).…”

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic–pituitary–adrenal axis hyperactivity

“…L-PGDS is produced in the choroid plexus and leptomeninges (Urade et al 1993) and has been well studied in association with the regulation of sleep-wake cycle (Qu et al 2006) and sensitivity to tactile pain (Eguchi et al 1999). It also plays a protective, anti-inflammatory role in some neurological disorders such as Alzheimer's disease (Kanekiyo et al 2007) and cerebral ischemia (Saleem et al 2009).…”