Expression of metabotropic glutamate receptors in rat meningeal and brain microvasculature and choroid plexus.
This study investigated the distribution of metabotropic glutamate receptors (mGluRs) in meningeal and parenchymal microvasculature and in choroid plexus by means of Western blot analysis and immunohistochemistry. Western blot analysis demonstrated mGluR expression in both rat and human leptomeningeal tissues. In the rat, mGluR expression was developmentally regulated, with only mGluR2/3 showing expression at the embryonic day 19 developmental stage. In contrast, mGluR1 alpha, mGluR2/3, mGluR4a, and mGluR7 were expressed in leptomeninges from adult rats. Immunohistochemical analyses showed intense mGluR1 alpha immunoreactivity in the pia mater and blood vessels in the subarachnoid space and in the arachnoid layer of the meninges. mGluR2/3, mGluR4a, mGluR5, and mGluR7 were also expressed in meningeal microvasculature. In addition, the parenchymal microvasculature and choroid plexus were strongly immunoreactive for mGluR1 alpha, mGluR2/3, mGluR4a, mGluR5, and mGluR7. We used antibodies specific for phenotypic markers of microvascular and glial cells to characterize the cell type(s) immunopositive for mGluRs. Comparison of staining with anti-von Willebrand factor antibody and anti-mGluR antibodies revealed that mGluR immunoreactivity was present in cells that surrounded the luminal surface labeled by the endothelial cell marker. In these cells, smooth muscle actin and mGluR immunoreactivity overlapped, suggesting that, in addition to endothelial cells, pericytes within the microvasculature also express mGluRs. Furthermore, expression of mGluR1 alpha was also observed in pure pericyte cultures isolated from bovine retina. These data suggest that glutamate by means of activation of mGluRs may have a broad sphere of physiological influence in the brain which in addition to modulating synaptic transmission may also have a role in determining microvascular function and dysfunction.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Samantha E
SE
Gillard
John
J
Tzaferis
Ho-Ching Tiffany
HC
Tsui
Ann E
AE
Kingston
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply*; D002417:Cattle; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D002831:Choroid Plexus / Q000098:blood supply*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008578:Meninges / Q000098:blood supply*; D008833:Microcirculation; D020286:Pericytes / Q000378:metabolism; D051381:Rats / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
D018094:Receptors, Metabotropic Glutamate