Murine Glut-1 transporter haploinsufficiency: postnatal deceleration of brain weight and reactive astrocytosis.
Neurobiol Dis
; 36(1): 60-9, 2009 Oct.
Article
in En
| MEDLINE
| ID: mdl-19591936
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Astrocytes
/
Gene Expression Regulation, Developmental
/
Glucose Transporter Type 1
/
Gliosis
Type of study:
Prognostic_studies
Language:
En
Journal:
Neurobiol Dis
Journal subject:
NEUROLOGIA
Year:
2009
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos