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http://dx.doi.org/10.14348/molcells.2015.0041

Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1-/- Mice  

Lim, Soo-Yeon (Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University)
Mah, Won (Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University)
Publication Information
Molecules and Cells / v.38, no.6, 2015 , pp. 540-547 More about this Journal
Abstract
Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2-3 months old) and juvenile (4 weeks old) $Git1^{\check{s}/\check{s}}$ mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in $Git1^{\check{s}/\check{s}}$ mice.
Keywords
ADHD; astrocytosis; basal ganglia; GIT1;
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