Glut1 and Glut3 expression, but not capillary density, is increased by cobalt chloride in rat cerebrum and retina

Treatment of rats with cobalt chloride [Co(LI)], an agent that stimulates t he expression of a set of hypoxia-responsive genes, for 10-12 days resulted in 1.45- and 1.40-fold increases in the content of Glut1 mRNA and Glut1 in cerebral gray matter, respectively (P < 0.05 for both changes). The increa se in Glut1 content was associated with a significant increase in the conte nt of Glut1 staining in microvessels isolated from cerebral gray matter, an d in the intensity of Glut1 in microvessels of the frontal lobe and hippoca mpus assessed by immunohistochemistry. The abundance of Glut3 in cerebrum o f Co(II)-treated rats also increased by 1.3-fold(P < 0.05), but the increas e was not associated with a change in the content of Glut3 mRNA. In retina, treatment with Co(II) resulted in 2.48- and 1.23-fold increases in the con tent of Glut1 mRNA and Glut1 protein, respectively (P < 0.05 for both chang es); similar increases in Glut1 protein expression were observed in isolate d retinal microvasculature. The content of Glut3 in retina also increased 1 .5-fold in Co(II)-treated rats (P < 0.05). In addition, treatment with Co(I I) resulted in a significant 2.2-fold increase in the expression of VEGF in the cerebrum. However, despite the Co(II)-induced increase in Glut1 expres sion in cerebral and retinal microvasculature and VEGF in cerebrum, there w as no increase in the capillary density in either tissue. It is concluded t hat a 10-12 day exposure to Co(II), presumably acting through the hypoxia-s ignaling pathway, results in enhanced expression of both major glucose tran sporters in cerebral cortex and retina, without increasing the capillary de nsity of either tissue. (C) 1999 Elsevier Science B.V. All rights reserved.