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Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease.

Kim HJ, Shin EJ, Lee BH, Choi SH, Jung SW, Cho IH, Hwang SH, Kim JY, Han JS, Chung C, Jang CG, Rhim H, Kim HC, Nah SY - Mol. Cells (2015)

Bottom Line: The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments.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.Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.

View Article: PubMed Central - PubMed

Affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.

ABSTRACT
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 [Ca(2+)]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca(2+)]i 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-β protein (Aβ)-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 Aβ and could be utilized for AD prevention or therapy.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the involvement of the cholinergic system in gintonin-mediated anti-Alzheimer’s disease (AD) through LPA receptor activation. In our previous report, we showed that gintonin attenuated amyloid plaque formation and ameliorated learning and memory dysfunctions (Hwang et al., 2012). In this study, we found that gintonin stimulates the cholinergic systems by acetylcholine release and the increase of ChAT expression and protective effects against acute Aβ-induced and long-term cholinergic dysfunctions in the transgenic AD animal model. Gintonin-mediated activation of LPA receptors could be coupled to anti-AD effects via dual actions of the non-amyloidogenic pathway and modulations of the cholinergic system in the brain according to the described pathways.
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f7-molce-38-9-796: Schematic diagram of the involvement of the cholinergic system in gintonin-mediated anti-Alzheimer’s disease (AD) through LPA receptor activation. In our previous report, we showed that gintonin attenuated amyloid plaque formation and ameliorated learning and memory dysfunctions (Hwang et al., 2012). In this study, we found that gintonin stimulates the cholinergic systems by acetylcholine release and the increase of ChAT expression and protective effects against acute Aβ-induced and long-term cholinergic dysfunctions in the transgenic AD animal model. Gintonin-mediated activation of LPA receptors could be coupled to anti-AD effects via dual actions of the non-amyloidogenic pathway and modulations of the cholinergic system in the brain according to the described pathways.

Mentions: The last possibility is that gintonin-mediated LPA receptor activation is coupled to dual signaling pathways. Gintonin-mediated activations of LPA receptor could induce acetylcholine release and increase acetylcholine synthesis as role of a lipid-derived neurotransmitter and/or tropic factor. Gintonin-mediated activations of LPA receptor could be also coupled to the stimulation of neurotrophic and neuroprotective sAPPα release in the hippocampus. Therefore, both gintonin-mediated maintenance of acetylcholine levels by restoring cholinergic systems under Aβ or scopolamine insult and gintonin-mediated beneficial sAPPα formation in nervous system might contribute to conserve cholinergic systems against Aβ and in the transgenic AD mouse model. Figure 7 shows a schematic diagram of how gintonin-mediated LPA receptor activations are coupled to anti-AD actions via stimulations of cholinergic systems and sAPPα formation.


Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease.

Kim HJ, Shin EJ, Lee BH, Choi SH, Jung SW, Cho IH, Hwang SH, Kim JY, Han JS, Chung C, Jang CG, Rhim H, Kim HC, Nah SY - Mol. Cells (2015)

Schematic diagram of the involvement of the cholinergic system in gintonin-mediated anti-Alzheimer’s disease (AD) through LPA receptor activation. In our previous report, we showed that gintonin attenuated amyloid plaque formation and ameliorated learning and memory dysfunctions (Hwang et al., 2012). In this study, we found that gintonin stimulates the cholinergic systems by acetylcholine release and the increase of ChAT expression and protective effects against acute Aβ-induced and long-term cholinergic dysfunctions in the transgenic AD animal model. Gintonin-mediated activation of LPA receptors could be coupled to anti-AD effects via dual actions of the non-amyloidogenic pathway and modulations of the cholinergic system in the brain according to the described pathways.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588723&req=5

f7-molce-38-9-796: Schematic diagram of the involvement of the cholinergic system in gintonin-mediated anti-Alzheimer’s disease (AD) through LPA receptor activation. In our previous report, we showed that gintonin attenuated amyloid plaque formation and ameliorated learning and memory dysfunctions (Hwang et al., 2012). In this study, we found that gintonin stimulates the cholinergic systems by acetylcholine release and the increase of ChAT expression and protective effects against acute Aβ-induced and long-term cholinergic dysfunctions in the transgenic AD animal model. Gintonin-mediated activation of LPA receptors could be coupled to anti-AD effects via dual actions of the non-amyloidogenic pathway and modulations of the cholinergic system in the brain according to the described pathways.
Mentions: The last possibility is that gintonin-mediated LPA receptor activation is coupled to dual signaling pathways. Gintonin-mediated activations of LPA receptor could induce acetylcholine release and increase acetylcholine synthesis as role of a lipid-derived neurotransmitter and/or tropic factor. Gintonin-mediated activations of LPA receptor could be also coupled to the stimulation of neurotrophic and neuroprotective sAPPα release in the hippocampus. Therefore, both gintonin-mediated maintenance of acetylcholine levels by restoring cholinergic systems under Aβ or scopolamine insult and gintonin-mediated beneficial sAPPα formation in nervous system might contribute to conserve cholinergic systems against Aβ and in the transgenic AD mouse model. Figure 7 shows a schematic diagram of how gintonin-mediated LPA receptor activations are coupled to anti-AD actions via stimulations of cholinergic systems and sAPPα formation.

Bottom Line: The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments.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.Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.

View Article: PubMed Central - PubMed

Affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.

ABSTRACT
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 [Ca(2+)]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca(2+)]i 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-β protein (Aβ)-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 Aβ and could be utilized for AD prevention or therapy.

No MeSH data available.


Related in: MedlinePlus