Central Administration of Ampelopsin A Isolated from Vitis vinifera Ameliorates Cognitive and Memory Function in a Scopolamine-Induced Dementia Model.

Yuni Hong,Soo-Jin Oh,Bonggi Lee,Shi Yong Ryu,Young-Eun Han,Ansoo Lee,Yun-Hyeok Choi,Chun Whan Choi,Min Soo Kim,Rebecca Magnan

doi:10.3390/antiox10060835

Abstract

Neurodegenerative diseases are characterized by the progressive degeneration of the function of the central nervous system or peripheral nervous system and the decline of cognition and memory abilities. The dysfunctions of the cognitive and memory battery are closely related to inhibitions of neurotrophic factor (BDNF) and brain-derived cAMP response element-binding protein (CREB) to associate with the cholinergic system and long-term potentiation. Vitis vinifera, the common grapevine, is viewed as the important dietary source of stilbenoids, particularly the widely-studied monomeric resveratrol to be used as a natural compound with wide-ranging therapeutic benefits on neurodegenerative diseases. Here we found that ampelopsin A is a major compound in V. vinifera and it has neuroprotective effects on experimental animals. Bath application of ampelopsin A (10 ng/µL) restores the long-term potentiation (LTP) impairment induced by scopolamine (100 μM) in hippocampal CA3-CA1 synapses. Based on these results, we administered the ampelopsin A (10 ng/µL, three times a week) into the third ventricle of the brain in C57BL/6 mice for a month. Chronic administration of ampelopsin A into the brain ameliorated cognitive memory-behaviors in mice given scopolamine (0.8 mg/kg, i.p.). Studies of mice’s hippocampi showed that the response of ampelopsin A was responsible for the restoration of the cholinergic deficits and molecular signal cascades via BDNF/CREB pathways. In conclusion, the central administration of ampelopsin A contributes to increasing neurocognitive and neuroprotective effects on intrinsic neuronal excitability and behaviors, partly through elevated BDNF/CREB-related signaling.

Highlights

This article is an open access articleAlzheimer’s disease (AD) is the most common neurodegenerative disease with progressive memory loss and cognitive decline in the elderly [1]
We examined whether the bath application of ampelopsin A to the brain rescues the scopolamine-induced deficit in hippocampal Long-term potentiation (LTP)
We examined whether central administration of ampelopsin A is responsible for antioxidant and anti-apoptotic effects

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disease with progressive memory loss and cognitive decline in the elderly [1]. The pathological hallmarks of AD include amyloid-β protein accumulation, tau protein aggregation, excessive oxidative stress, and cholinergic dysfunction [2]. Cholinergic circuits have been implicated in cognitive functioning, especially in hippocampus-dependent memory formation, through distributed under the terms and conditions of the Creative Commons. Antioxidants 2021, 10, 835 the modulation of hippocampal synaptic plasticity and transmission [3]. Acetylcholinesterase (AChE) inhibitors, such as donepezil, have become major therapeutic targets for AD treatment, by increasing the availability of ACh at cholinergic synapses within a short period [5]. The benefits of current treatments remain controversial due to their lack of efficacy and critical side-effect for long-term use [6]

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