Human Neuroepithelial Cells Express NMDA Receptors

Abstract

L-glutamate, an excitatory neurotransmitter, binds to both ionotropic and metabotropic glutamate receptors. In certain parts of the brain the BBB contains two normally impermeable barriers: 1) cerebral endothelial barrier and 2) cerebral epithelial barrier. Human cerebral endothelial cells express NMDA receptors; however, to date, human cerebral epithelial cells (neuroepithelial cells) have not been shown to express NMDA receptor message or protein. In this study, human hypothalamic sections were examined for NMDA receptors (NMDAR) expression via immunohistochemistry and murine neuroepithelial cell line (V1) were examined for NMDAR via RT-PCR and Western analysis. We found that human cerebral epithelium express protein and cultured mouse neuroepithelial cells express both mRNA and protein for the NMDA receptor. These findings may have important consequences for neuroepithelial responses during excitotoxicity and in disease.

Proteomic Analysis of Human Cerebral Endothelial Cells Activated by Glutamate/MK-801: Significance in Ischemic Stroke Injury

“…The expression of GDH by cerebral endothelial cells has not been reported previously. This apparent regulation of GDH expression in CECs in response to glutamate receptor activation (and apparently blockade) suggests that any glutamate receptor activity could modulate GDH as a protective response mounted by CECs to lessen the toxic effects of glutamate, possibly via NMDA as well as other glutamate receptors (Sharp et al 2003a(Sharp et al , b, 2005. Protein 14-3-3 14-3-3 proteins are highly conserved cytosolic proteins which mediate signal transduction, cell cycle regulation, and apoptosis (Satoh et al 2004).…”

“…Our laboratory's recent characterization of NMDA receptors on human and mouse cerebral endothelial cells, as well as neuroepithelial cells, by western blotting, polymerase chain reaction, and functional studies suggests that glutamate participates in BBB dysregulation by increasing endothelial calcium (Sharp et al 2003a(Sharp et al , b, 2005. This results in a loss of junctional integrity and solute barrier through mitochondrial stress and oxidant formation (Love 1999;Sharp et al 2003aSharp et al , b, 2005.…”

“…This results in a loss of junctional integrity and solute barrier through mitochondrial stress and oxidant formation (Love 1999;Sharp et al 2003aSharp et al , b, 2005. Mechanistically, NMDA-Ca 2+ -induced oxidant formation in experimental models of brain endothelial cells produces a stress which appears to replicate the events in neuronal excitotoxicity (Facchinetti et al 1998;Ciani et al 1996).…”

“…Excitotoxicity represents extreme cell stress or death brought about by overstimulation of these receptors via calcium influx (Hansen 1985;Zhang and Lipton 1999) and oxidant formation (Imaizumi et al 1996), usually considered an exclusively neuronal pathology. However, NMDA receptors are also present on keratinocytes (Nahm et al 2004), megakaryocytes (Hitchcock et al 2003), neuroepithelium, and the endothelium (Sharp et al 2003a(Sharp et al , b, 2005. Based on capillary endothelial expression of NMDA receptors, it has been suggested that glutamate-NMDA receptors present on capillaries contribute to the development of postischemic brain edema (Simon et al 1984).…”

Immuno-psychiatry: an agenda for clinical practice and innovative research

“…Thus, alterations in NMDAR signalling might directly confer risk for psychosis and diabetes. In addition, NMDAR is also expressed at the surface of epithelial barrier cells [49], monocytes [50] and lymphocytes [51], potentially regulating biological barriers and immune reactions. Finally, NMDAR is expressed by cardiac myocytes and cells of the basolateral proximal tubule in the kidney, and its activation in these systems produces important cellular and organ regulation (see [52] for a review).…”