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KMID : 0613820180280050597
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Journal of Life Science
2018 Volume.28 No. 5 p.597 ~ p.604
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Analysis of Gliotransmitters in ADHD Mice
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Kim Ga-Yeon
Park Jae-Won
Yoon Bo-Eun
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Abstract
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Although the core mechanisms of Attention Deficit/Hyperactivity Disorder (ADHD) are unknown, several ADHD-associated proteins have been studied. G-protein?coupled receptor kinase interacting protein-1 (GIT1) is a multifunctional adapter protein that affects neuron growth and dendrite formation. GIT1-deficient mice have shown ADHD-like behavior and also recovered through amphetamine treatment. In this study, gliotransmitters were investigated in both intracellular and extracellular space from GIT1-deficient mice. To measure the amount of gliotransmitters, primary astrocyte cultures were taken from the cerebral and cerebellar cortices of wild (WT), hetero (HE), and knock-out (KO) mice. Major gliotransmitters were analyzed using high-performance liquid chromatography. It was observed that the amount of excitatory and inhibitory gliotransmitters were dependent on genotype and showed a change in excitation/inhibition ratios. Interestingly, the major excitatory gliotransmitter, glutamate, existed at the lowest level in WT mice, but the amount of inhibitory gliotransmitters, gamma-aminobutyric acid (GABA) and glycine, varied depending on brain region. Remarkably, an increased amount of GABA was measured at the intracellular cerebrum in WT mice compared with KO mice. It was presumed that KO mice would secrete more inhibitory gliotransmitters to compensate for GIT1 depletion or else acquire a defect to reuptake-secreted GABA. This may be a possible mechanism for ADHD pathology.
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KEYWORD
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ADHD, astrocyte, GIT1, glia, gliotransmitter
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