Type 1 diabetes alters astrocytic properties related with neurotransmitter supply, causing abnormal neuronal activities

Abstract

Glutamine synthetase (GS), an astrocytic protein in the brain, mediates the process by which glutamate (Glu) is transformed into glutamine (Gin) during Glu and gammaaminobutyric acid (GABA) de nouo synthesis. There are many types of neural complications related with those neurotransmitters in type 1 diabetes (T1D) patients, but there is little information about the change GS. Therefore, we examined changes in GS activity and expression, as well as the amount of Glu, Gln, and GABA in the brain of a T1D animal model. Using primary culture we found that glucose fluctuation caused glial fibrillary acidic protein (GFAP) and GS changes but constant high glucose level didn't. In T1D mouse, GS expression increased in the prefrontal cortex (PFq and hippocampus (HI), but decreased GS activity was only observed in the HI whereas GFAP expression decreased in both regions. Gln increased in both regions, but Glu and GABA were only increased in the HI of T1D animals where GS activity decreased with higher reactive oxygen/nitrogen species. Collectively, low GS activity may be closely related with high levels of Glu and GABA in the HI of T1D brain, and this would result in abnormal neurotransmissions. (C) 2015 Elsevier B.V. All rights reserved.