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

Lim, Soo-Yeon; Mah, Won

doi:10.14348/molcells.2015.0041

[국내논문] Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1-/- Mice 원문보기

Molecules and cells, v.38 no.6, 2015년, pp.540 - 547

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)

Abstract ▼ AI-Helper

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.

주제어

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가설 설정

(C) Neuronal densities in the GP, TRN, Ctx, and VB are not affected in Git1−/− mice.
We hypothesized that the ADHD-like symptoms in Git1−/− mice may involve local changes in specific brain circuits.

제안 방법

For quantitative analysis, images were captured with a confocal microscope (63× and 20× objectives; Leica Microsystems) and analyzed using Metamorph (Molecular Devices).

성능/효과

In conclusion, we have observed severe astrocytosis and an altered expression of GABA and parvalbumin in the brain regions related to basal ganglia circuitry in Git1−/− mice.
These results suggest that neurons in the GP of Git1−/− mice may show decreased glutamatergic transmission and increased GABAergic transmission, the latter of which was reflected by increased GABA in the GP in this study.

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