Elsevier

Neuroscience

Volume 146, Issue 3, 25 May 2007, Pages 1150-1157
Neuroscience

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

https://doi.org/10.1016/j.neuroscience.2007.02.042Get rights and content

Abstract

Prostaglandins (PGs) are bioactive lipid mediators released following brain hypoxic–ischemic injury. Clearance and re-uptake of these prostaglandins occur via a transmembrane prostaglandin transporter (PGT), which exchanges PG for lactate. We used Western blot analyses to examine the PGT developmental profile and its regional distribution as well as changes in transporter expression during chronic hypoxia in the neonatal mouse brain. Microsomal preparations from four brain regions (cortex, hippocampus, cerebellum and brainstem/diencephalon) showed gradual increases in prostaglandin transporter expression in all brain regions examined from postnatal day 1 till day 30. There was a significant regional heterogeneity in the prostaglandin transporter expression with highest expression in the cortex, followed by cerebellum and hippocampus, and least expressed in the brainstem/diencephalon. To further delineate the pattern of prostaglandin transporter expression, separate astrocytic and neuronal microsomal preparations were also examined. In contrast to neurons, which had a robust expression of prostaglandin transporters, astrocytes had very little PGT expression under basal conditions. In response to chronic hypoxia, there was a significant decline in PGT expression in vivo and in neurons in vitro, whereas cultured astrocytes increased their PGT expression. This is the first report on PGT expression in the CNS and our studies suggest that PGTs have 1) a widespread distribution in the CNS; 2) a gradual increase and a differential expression in various regions during brain development; and 3) striking contrast in expression between glia and neurons, especially in response to hypoxia. Since PGTs play a role as prostaglandin–lactate exchangers, we hypothesize that PGTs are important in the CNS during stress such as hypoxia.

Section snippets

Animals

Pregnant CD-1 mice were obtained from Charles River (Wilmington, DE, USA). Care was exercised in the handling of these animals and the minimal number of animals that was absolutely required was used in this study. This study was conducted in conformity with the Guiding Principles for Research Involving Animals and Human Beings and was approved by the Albert Einstein Animal Care and Use Committee (IACUC). Animal experiments were carried out in accordance with the National Institutes of Health

Regional PGT expression in adult mouse CNS

Western blot analysis revealed a heterogeneous regional distribution of PGT in the brain. In P30 mice, the anti-PGT antibody recognized a strong band at 65 kDa (Fig. 1A). Competition studies of the PGT with a synthetic peptide verified the specificity of this antibody (Fig. 1C). Relative expression was quantitated, with the predominant expression of PGT occurring in the CX, followed by the CB and HC, with the least expression in the BD (CX>CB=HC>BD) (Fig. 1B). Average PGT/actin was similar in

Discussion

In this study we have made a number of salient observations. First, in adult mouse brain, PGT is present in all the regions studied. Second, we used in our experiments microsomal preparations from four different brain regions (CX, HC, CB and BD) and demonstrated that the CX has the highest expression of PGT in the mouse brain. We would like to note that PGT expression may be highly coordinated with the synthesis and release of PGs since Bao et al. (2002) have shown that PGT expression is

Acknowledgments

We would like to thank Dr. Victor L. Schuster for suggestions and helpful discussions. We are also grateful for the excellent technical assistance of Mary Catherine Muenker. Supported by NIH 5P01HD32573 (G.G.H.).

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    Present address: G. G. Haddad, Pediatrics and Neuroscience, University of California, San Diego, Rady Children's Hospital of San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0735, USA.

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