Figure 4: Early Glut1 repletion mitigates the Glut1 DS disease phenotype in model mice. | Nature Communications

Figure 4: Early Glut1 repletion mitigates the Glut1 DS disease phenotype in model mice.

From: Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein

Figure 4

(a,b) Systemically administered AAV9-Glut1 results in a significant improvement in motor performance on (a) the rotarod and (b) in a vertical pole assay. N≥16 mice in each cohort. (c) Quantification of RNA (endothelial and astrocytic) expression in brain tissue of controls and mutants treated on PND3. N≥5 mice in each cohort. (d) Representative western blot analysis of Glut1 protein in brain tissue of Glut1 DS mutants following repletion of the protein. The lower set of blots demonstrates that repletion of Glut1 by the virus raises the 45 kDa (astrocytic) as well as 55 kDa (endothelial) differentially glycosylated isoforms of the protein. (e) Quantitative assessment of total protein (astrocytic and endothelial) in treated mutants and control mice. N≥4 mice each. (f,g) CSF, but not blood glucose levels are significantly increased in mutants treated with AAV9-Glut1; a corresponding increase in the ratio of CSF:Blood glucose was assessed. N≥13 mice in each cohort. (h) Microcephaly is ameliorated in mutants restored for Glut1 protein. N≥7 mice in each cohort. Note: *, **, ***, P<0.05, P<0.01, P<0.001 respectively, one-way ANOVA for each panel in the figure.

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