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

• We confirmed alterations of GS in the brain of STZ-induced T1D mice.
• The activity of GS was lower in the HI although the expression higher than CTL.
• Glu level increased in the HI being related with the lower GS activity.
• The increased ROS/RNS levels in HI may be a cause of the lower GS activity.

Glutamine synthetase (GS), an astrocytic protein in the brain, mediates the process by which glutamate (Glu) is transformed into glutamine (Gln) during Glu and gamma-aminobutyric acid (GABA) de novo 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 (PFC) 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.