UMMS Affiliation

Department of Microbiology and Physiological Systems; Horae Gene Therapy Center

Date

1-20-2017

Document Type

Article

Disciplines

Cellular and Molecular Physiology | Developmental Neuroscience | Nervous System Diseases | Neurology

Abstract

Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood-brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS.

Rights and Permissions

Copyright © 2017, The Author(s). Citation: Nat Commun. 2017 Jan 20;8:14152. doi: 10.1038/ncomms14152. Link to article on publisher's site

DOI of Published Version

10.1038/ncomms14152

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

Journal Title

Nature communications

PubMed ID

28106060

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

 
 

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