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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

Effect of gintonin (GT; 25 or 50 mg/kg, p.o.) on cholinergic system changes. (A) Experimental schedule to evaluate the long-term effect of gintonin on cholinergic system impairment in the APPswe/PSEN-1 double Tg mouse. (B) Acetylcholine level, (C) acetylcholinesterase activity, and choline acetyltransferase activity in the hippocampus of the APPswe/PSEN-1 double Tg mouse. Donepezil (DPZ; 1 mg/kg, i.p.) was used as a reference drug. Sal = saline. Each value is the mean ± S.E.M of four mice. #P < 0.05, ##P < 0.01 vs. Sal (one-way ANOVA followed by Fisher’s PLSD test).
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f5-molce-38-9-796: Effect of gintonin (GT; 25 or 50 mg/kg, p.o.) on cholinergic system changes. (A) Experimental schedule to evaluate the long-term effect of gintonin on cholinergic system impairment in the APPswe/PSEN-1 double Tg mouse. (B) Acetylcholine level, (C) acetylcholinesterase activity, and choline acetyltransferase activity in the hippocampus of the APPswe/PSEN-1 double Tg mouse. Donepezil (DPZ; 1 mg/kg, i.p.) was used as a reference drug. Sal = saline. Each value is the mean ± S.E.M of four mice. #P < 0.05, ##P < 0.01 vs. Sal (one-way ANOVA followed by Fisher’s PLSD test).

Mentions: The long-term effects of gintonin on the level of acetylcholine and activities of AChE and ChAT in the APPswe/PSEN-1 double Tg mice were examined according to the procedure described in Fig. 5A. Chronic treatment with gintonin (25 or 50 mg/kg, p.o., thrice a week for 3 months) significantly increased acetylcholine levels (25 or 50 mg/kg gintonin vs. Sal, #P < 0.05 or ##P < 0.01) (Fig. 5B) and ChAT activity (25 or 50 mg/kg gintonin vs. Sal, #P < 0.05 or ##P < 0.01), but significantly decreased AChE activity in the hippocampus of the APPswe/PSEN-1 double Tg mice (25 or 50 mg/kg gintonin vs. Sal, #P < 0.05 or ##P < 0.01) (Fig. 5C), indicating that gintonin improves the hippocampal cholinergic function in the AD model mice. The effect of gintonin on the hippocampal cholinergic function of APPswe/PSEN-1 double Tg mice was comparable to that of donepezil (1 mg/kg, thrice a week for 3 months), and these results are in accordance with those observed in the acute Aβ (1–40)-treated mice (Fig. 5).


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)

Effect of gintonin (GT; 25 or 50 mg/kg, p.o.) on cholinergic system changes. (A) Experimental schedule to evaluate the long-term effect of gintonin on cholinergic system impairment in the APPswe/PSEN-1 double Tg mouse. (B) Acetylcholine level, (C) acetylcholinesterase activity, and choline acetyltransferase activity in the hippocampus of the APPswe/PSEN-1 double Tg mouse. Donepezil (DPZ; 1 mg/kg, i.p.) was used as a reference drug. Sal = saline. Each value is the mean ± S.E.M of four mice. #P < 0.05, ##P < 0.01 vs. Sal (one-way ANOVA followed by Fisher’s PLSD test).
© Copyright Policy
Related In: Results  -  Collection

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

f5-molce-38-9-796: Effect of gintonin (GT; 25 or 50 mg/kg, p.o.) on cholinergic system changes. (A) Experimental schedule to evaluate the long-term effect of gintonin on cholinergic system impairment in the APPswe/PSEN-1 double Tg mouse. (B) Acetylcholine level, (C) acetylcholinesterase activity, and choline acetyltransferase activity in the hippocampus of the APPswe/PSEN-1 double Tg mouse. Donepezil (DPZ; 1 mg/kg, i.p.) was used as a reference drug. Sal = saline. Each value is the mean ± S.E.M of four mice. #P < 0.05, ##P < 0.01 vs. Sal (one-way ANOVA followed by Fisher’s PLSD test).
Mentions: The long-term effects of gintonin on the level of acetylcholine and activities of AChE and ChAT in the APPswe/PSEN-1 double Tg mice were examined according to the procedure described in Fig. 5A. Chronic treatment with gintonin (25 or 50 mg/kg, p.o., thrice a week for 3 months) significantly increased acetylcholine levels (25 or 50 mg/kg gintonin vs. Sal, #P < 0.05 or ##P < 0.01) (Fig. 5B) and ChAT activity (25 or 50 mg/kg gintonin vs. Sal, #P < 0.05 or ##P < 0.01), but significantly decreased AChE activity in the hippocampus of the APPswe/PSEN-1 double Tg mice (25 or 50 mg/kg gintonin vs. Sal, #P < 0.05 or ##P < 0.01) (Fig. 5C), indicating that gintonin improves the hippocampal cholinergic function in the AD model mice. The effect of gintonin on the hippocampal cholinergic function of APPswe/PSEN-1 double Tg mice was comparable to that of donepezil (1 mg/kg, thrice a week for 3 months), and these results are in accordance with those observed in the acute Aβ (1–40)-treated mice (Fig. 5).

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