Glut1/SLC2A1 is crucial for the development of the blood‐brain barrier in vivo

Abstract

The data suggest a crucial role of Glut1 in the development of the cerebral endothelial cells with BBB properties in vivo. The findings suggest that modulation of Glut1 expression and function may open new directions of research for therapeutic strategies to prevent vasogenic brain edema.

GLUT3 gene expression is critical for embryonic growth, brain development and survival

“…Again, GLUT1 has a similar pattern of expression with additional pronounced expression in the developing kidney (pronephric ducts). By 36 hpf, GLUT3 and GLUT1 show expression that is restricted to the brain, with GLUT1 being more caudal and ventral, restricted to endothelial cells as shown previously (27), and GLUT3 being more rostral and dorsal restricted to the neuronal compartment, with GLUT1 continuing to have robust expression in the developing kidney, and GLUT3 expression observed in the dorsal spinal neurons and gastro-intestinal tract.…”

“…Additional studies reveal that impaired GLUT1 expression resulted in a loss of cerebral endothelial cells with concomitant down-regulation of junctional proteins important for intact adherens and tight junctions that impaired cerebral circulation. This leaky blood-brain barrier caused vasogenic brain edema (27). In addition, abrogation of the anti-apoptotic kinase, Akt2, results in a phenotype strikingly similar to the glut1 morphant.…”

Defect of development of ocular vasculature in Glut1/SLC2A1 knockdown in vivo

“…All the experimental processes are similar to those described before. 10 The pattern of Glut1 expression in the zebrafish eye (Fig. 1A) appears similar to that in the mammalian eyes.…”

“…8,9 In our zebrafish model of Glut1 knockdown, a defective development of the function and structure of the blood-brain barrier (BBB) with consequent vasogenic brain edema has been identified. 10 To date, there is no information on the role of Glut1 during the development of the Defect of development of ocular vasculature in Glut1/SLC2A1 knockdown in vivo 10 Embryos/larvae (n = 166) of developing time points 2 to 4 days postfertilization (dpf) were used for this study. All the experimental processes are similar to those described before.…”

Sinus venosus defect (SVD) identified in zebrafish Glut1 morphants by video imaging

“…In our zebrafish Glut1 knockdown model, we have investigated the in vivo effects on the development of blood-brain barrier (BBB) [2]. Here we show that the structural integrity of SV is dynamically perturbed in this model, manifested as an initial rupture of SV (Video 2) followed by a progressive bleeding (Video 3) in contrast to the control (Video 1).…”