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Murine Glut-1 transporter haploinsufficiency: postnatal deceleration of brain weight and reactive astrocytosis.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2009 Oct; Vol. 36 (1), pp. 60-9. Date of Electronic Publication: 2009 Jul 08. - Publication Year :
- 2009
-
Abstract
- Glucose transporter type 1 (Glut-1) facilitates glucose flux across the blood-brain-barrier. In humans, Glut-1 deficiency causes acquired microcephaly, seizures and ataxia, which are recapitulated in our Glut-1 haploinsufficient mouse model. Postnatal brain weight deceleration and development of reactive astrogliosis were significant by P21 in Glut-1(+/-) mice. The brain weight differences remained constant after P21 whereas the reactive astrocytosis continued to increase and peaked at P90. Brain immunoblots showed increased phospho-mTOR and decreased phospho-GSK3-beta by P14. After fasting, the mature Glut-1(+/-) females showed a trend towards elevated phospho-GSK3-beta, a possible neuroprotective response. Lithium chloride treatment of human skin fibroblasts from control and Glut-1 DS patients produced a 45% increase in glucose uptake. Brain imaging of mature Glut-1(+/-) mice revealed a significantly decreased hippocampal volume. These subtle immunochemical changes reflect chronic nutrient deficiency during brain development and represent the experimental correlates to the human neurological phenotype associated with Glut-1 DS.
- Subjects :
- Age Factors
Animals
Animals, Newborn
Apoptosis genetics
Astrocytes metabolism
Body Weight genetics
Carbohydrate Metabolism, Inborn Errors genetics
Carbohydrate Metabolism, Inborn Errors pathology
Carrier Proteins metabolism
Cell Proliferation
Cell Size
Cells, Cultured
Dendrites pathology
Disease Models, Animal
Female
Fibroblasts drug effects
Gene Expression Regulation, Developmental drug effects
Glial Fibrillary Acidic Protein metabolism
Gliosis genetics
Gliosis metabolism
Glucose Transporter Type 1 genetics
Humans
Hypoglycemia genetics
Hypoglycemia pathology
Hypoglycemia physiopathology
In Situ Nick-End Labeling methods
Lithium Chloride pharmacology
Magnetic Resonance Imaging methods
Male
Mice
Mice, Knockout
Neurons pathology
Organ Size genetics
Phosphotransferases (Alcohol Group Acceptor) metabolism
Signal Transduction genetics
Skin cytology
TOR Serine-Threonine Kinases
Astrocytes pathology
Brain growth & development
Brain pathology
Gene Expression Regulation, Developmental genetics
Gliosis pathology
Glucose Transporter Type 1 deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 36
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 19591936
- Full Text :
- https://doi.org/10.1016/j.nbd.2009.06.014