Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease
- Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease
- 임혜원; 김현중; 신은주; 이병환; 최선혜; 정석원; 조익현; 황성희; 김준용; 한정수; 정지혜; 장춘곤; 김형춘; 나승열
- Issue Date
- Molecules and cells
- VOL 38, NO 9-805
- Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced [Ca2+], transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca2+], transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 2 weeks) also significantly attenuated amyloid-beta protein (A)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to A beta and could be utilized for AD prevention or therapy.
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