• 생명과학회지
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• 제28권5호
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• pp.597-604
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• 2018

ADHD (Attention Deficit/Hyperactivity Disorder)은 4-17세의 아동 및 청소년의 약 10%가 겪는 흔한 신경 발달 장애이지만 그 핵심 기전이 알려져 있지 않은 가운데 관련한 여러 단백질들이 보고되어왔다. 이중 GIT1 (G-protein coupled-receptor kinase interacting protein-1)은 중추신경계에서 dendritic spine formation와 growth에 영향을 미치는 multifunctional adaptor protein으로, GIT1이 제거된 생쥐는 과잉행동, 주의력결핍 그리고 충동성을 보이는 ADHD 증상을 보이게 된다. 이 논문에서는 GIT1 유전자 변형 생쥐를 이용하여 genotype별로 신경교세포의 전달물질(gliotransmitter)을 비교 분석하는 실험을 진행하였다. 그 결과 주요 흥분성 전달물질인 glutamate는 HE (hetero)와 KO (knock-out)의 세포 내에서 WT (wildtype)보다 더 높은 농도로 존재했다. 한편, 억제성 신경전달물질인 GABA와 glycine의 경우 전반적으로 HE에서 가장 많은 함유량을 보였지만 소뇌 세포내의 경우, KO이 WT보다 많은 양을 함유한 것에 비해 대뇌 세포 내에서는 KO보다 WT의 억제성 전달물질 함유량이 높았다. 또한, glutamate와 GABA를 기준으로 흥분성/억제성 비율(excitation/inhibition ratio)을 보았을 때, 소뇌 세포 내/외 모두에서 KO이 가장 높은 수치를 보였고, 대뇌에서는 세포 내/외 모두 HE에서 가장 높은 수치를 보였다. 억제성 신경전달물질인 GABA가 KO의 대뇌 세포 외에서 가장 많은 것으로 보아 GIT1 결손을 보완하기 위해 억제성 물질을 더 많이 분비하거나 또는 과도하게 분비된 GABA를 재흡수하지 못하는 것이라 사료된다. 이는 ADHD 병리기전으로써 기능할 가능성을 제시하며 후속 연구를 통해 해당 기전에 대한 규명이 필요할 것으로 보인다.

• Molecules and Cells
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• 제45권2호
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• pp.65-75
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• 2022

Hypothalamus is a brain region that controls food intake and energy expenditure while sensing signals that convey information about energy status. Within the hypothalamus, molecularly and functionally distinct neurons work in concert under physiological conditions. However, under pathological conditions such as in diet-induced obesity (DIO) model, these neurons show dysfunctional firing patterns and distorted regulation by neurotransmitters and neurohormones. Concurrently, resident glial cells including astrocytes dramatically transform into reactive states. In particular, it has been reported that reactive astrogliosis is observed in the hypothalamus, along with various neuroinflammatory signals. However, how the reactive astrocytes control and modulate DIO by influencing neighboring neurons is not well understood. Recently, new lines of evidence have emerged indicating that these reactive astrocytes directly contribute to the pathology of obesity by synthesizing and tonically releasing the major inhibitory transmitter GABA. The released GABA strongly inhibits the neighboring neurons that control energy expenditure. These surprising findings shed light on the interplay between reactive astrocytes and neighboring neurons in the hypothalamus. This review summarizes recent discoveries related to the functions of hypothalamic reactive astrocytes in obesity and raises new potential therapeutic targets against obesity.

• Journal of Ginseng Research
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• 제43권2호
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• pp.305-311
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• 2019

Background: Gintonin is a ginseng-derived exogenous ligand of the G protein-coupled lysophosphatidic acid (LPA) receptor. We previously reported that gintonin stimulates gliotransmitter release in primary cortical astrocytes. Astrocytes play key roles in the functions of neurovascular systems. Although vascular endothelial growth factor (VEGF) is known to influence the normal growth and maintenance of cranial blood vessels and the nervous system, there is little information about the effect of gintonin on VEGF regulation in primary astrocytes, under normal and hypoxic conditions. Methods: Using primary cortical astrocytes of mice, the effects of gintonin on the release, expression, and distribution of VEGF were examined. We further investigated whether the gintonin-mediated VEGF release protects astrocytes from hypoxia. Results: Gintonin administration stimulated the release and expression of VEGF from astrocytes in a concentration- and time-dependent manner. The gintonin-mediated increase in the release of VEGF was inhibited by the LPA1/3 receptor antagonist, Ki16425; phospholipase C inhibitor, U73122; inositol 1,4,5- triphosphate receptor antagonist, 2-APB; and intracellular $Ca^{2+}$ chelator, BAPTA. Hypoxia further stimulated astrocytic VEGF release. Gintonin treatment stimulated additional VEGF release and restored cell viability that had decreased due to hypoxia, via the VEGF receptor pathway. Altogether, the regulation of VEGF release and expression and astrocytic protection mediated by gintonin under hypoxia are achieved via the LPA receptor-VEGF signaling pathways. Conclusion: The present study shows that the gintonin-mediated regulation of VEGF in cortical astrocytes might be neuroprotective against hypoxic insults and could explain the molecular basis of the beneficial effects of ginseng on the central nervous system.