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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

Effects of gintonin-enriched fraction (GEF) on scopolamine-induced memory deficit in the passive avoidance (A) and Morris water maze tests (B, C). (A) GEF (25, 50, and 100 mg/kg, p.o.) was daily administered through oral administration for three weeks. Memory impairment was induced by treatment with scopolamine (0.5 mg/kg, i.p.). Values are expressed as means ± SEM (n = 10). *P < 0.01 vs. control vehicle group). #P < 0.05 vs. scopolamine-treated control group. (B, C) The first trial session was performed 30 min after treatment with scopolamine. The training trial and the probe trial sessions were performed for 4 days as described in the Materials and Methods. Values are expressed as means ± SEM (n = 10). Mice were treated with GEF for 3 weeks by oral administration. *P < 0.01 vs. control vehicle group. #P < 0.05 vs. scopolamine-treated group.
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f2-molce-38-9-796: Effects of gintonin-enriched fraction (GEF) on scopolamine-induced memory deficit in the passive avoidance (A) and Morris water maze tests (B, C). (A) GEF (25, 50, and 100 mg/kg, p.o.) was daily administered through oral administration for three weeks. Memory impairment was induced by treatment with scopolamine (0.5 mg/kg, i.p.). Values are expressed as means ± SEM (n = 10). *P < 0.01 vs. control vehicle group). #P < 0.05 vs. scopolamine-treated control group. (B, C) The first trial session was performed 30 min after treatment with scopolamine. The training trial and the probe trial sessions were performed for 4 days as described in the Materials and Methods. Values are expressed as means ± SEM (n = 10). Mice were treated with GEF for 3 weeks by oral administration. *P < 0.01 vs. control vehicle group. #P < 0.05 vs. scopolamine-treated group.

Mentions: Next, we examined whether oral administration of gintonin-enriched fraction could ameliorate scopolamine-induced memory dysfunction. As shown in Fig. 2A, the effect of gintonin on memory function was first examined in a passive avoidance test. Treatment with scopolamine alone decreased the step-through latency time (Fig. 2A, *P < 0.01, compared with control vehicle), whereas the gintonin-enriched fraction treatment groups (25, 50, and 100 mg/kg, p.o.) demonstrated significantly improved latency times in a dose-dependent manner compared with the control group (Fig. 2A, #P < 0.05, compared with control). In addition, we also measured the effects of gintonin-enriched fraction using the Morris water maze task (Figs. 2B and 2C). The scopolamine-treated group exhibited longer escape latencies throughout the training days than the control vehicle group (*P < 0.01). The gintonin-enriched fraction significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of the training trial sessions in a dose-dependent manner (#P < 0.05, compared with scopolamine treatment group) (Fig. 2B). On the day following the final day of the training trial sessions, swimming times within the platform quadrant for the scopolamine-treated group were significantly lower than those of the control vehicle group (*P < 0.01). However, treatment with gintonin-enriched fraction significantly increased the swimming time shortened by scopolamine (#P < 0.05) (Fig. 2C). These results indicate that oral administration of gintonin-enriched fraction ameliorates scopolamine-induced memory dysfunctions.


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)

Effects of gintonin-enriched fraction (GEF) on scopolamine-induced memory deficit in the passive avoidance (A) and Morris water maze tests (B, C). (A) GEF (25, 50, and 100 mg/kg, p.o.) was daily administered through oral administration for three weeks. Memory impairment was induced by treatment with scopolamine (0.5 mg/kg, i.p.). Values are expressed as means ± SEM (n = 10). *P < 0.01 vs. control vehicle group). #P < 0.05 vs. scopolamine-treated control group. (B, C) The first trial session was performed 30 min after treatment with scopolamine. The training trial and the probe trial sessions were performed for 4 days as described in the Materials and Methods. Values are expressed as means ± SEM (n = 10). Mice were treated with GEF for 3 weeks by oral administration. *P < 0.01 vs. control vehicle group. #P < 0.05 vs. scopolamine-treated group.
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Related In: Results  -  Collection

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

f2-molce-38-9-796: Effects of gintonin-enriched fraction (GEF) on scopolamine-induced memory deficit in the passive avoidance (A) and Morris water maze tests (B, C). (A) GEF (25, 50, and 100 mg/kg, p.o.) was daily administered through oral administration for three weeks. Memory impairment was induced by treatment with scopolamine (0.5 mg/kg, i.p.). Values are expressed as means ± SEM (n = 10). *P < 0.01 vs. control vehicle group). #P < 0.05 vs. scopolamine-treated control group. (B, C) The first trial session was performed 30 min after treatment with scopolamine. The training trial and the probe trial sessions were performed for 4 days as described in the Materials and Methods. Values are expressed as means ± SEM (n = 10). Mice were treated with GEF for 3 weeks by oral administration. *P < 0.01 vs. control vehicle group. #P < 0.05 vs. scopolamine-treated group.
Mentions: Next, we examined whether oral administration of gintonin-enriched fraction could ameliorate scopolamine-induced memory dysfunction. As shown in Fig. 2A, the effect of gintonin on memory function was first examined in a passive avoidance test. Treatment with scopolamine alone decreased the step-through latency time (Fig. 2A, *P < 0.01, compared with control vehicle), whereas the gintonin-enriched fraction treatment groups (25, 50, and 100 mg/kg, p.o.) demonstrated significantly improved latency times in a dose-dependent manner compared with the control group (Fig. 2A, #P < 0.05, compared with control). In addition, we also measured the effects of gintonin-enriched fraction using the Morris water maze task (Figs. 2B and 2C). The scopolamine-treated group exhibited longer escape latencies throughout the training days than the control vehicle group (*P < 0.01). The gintonin-enriched fraction significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of the training trial sessions in a dose-dependent manner (#P < 0.05, compared with scopolamine treatment group) (Fig. 2B). On the day following the final day of the training trial sessions, swimming times within the platform quadrant for the scopolamine-treated group were significantly lower than those of the control vehicle group (*P < 0.01). However, treatment with gintonin-enriched fraction significantly increased the swimming time shortened by scopolamine (#P < 0.05) (Fig. 2C). These results indicate that oral administration of gintonin-enriched fraction ameliorates scopolamine-induced memory dysfunctions.

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