title: Anemoside A3 Enhances Cognition through the Regulation of Synaptic Function and Neuroprotection.
abstract: Compounds that have the ability to both strengthen synaptic function and facilitate neuroprotection are valuable cognitive enhancers that may improve health and quality of life, as well as retard age-related cognitive deterioration. Medicinal plants are an abundant source of potential cognitive enhancers. Here we report that anemoside A3 (AA3) isolated from Pulsatilla chinensis modulates synaptic connectivity in circuits central to memory enhancement. AA3 specifically modulates the function of AMPA-type glutamate receptors (AMPARs) by increasing serine phosphorylation within the GluA1 subunit, which is a modification required for the trafficking of GluA1-containing AMPARs to synapses. Furthermore, AA3 administration activates several synaptic signaling molecules and increases protein expressions of the neurotrophin brain-derived neurotrophic factor and monoamine neurotransmitters in the mouse hippocampus. In addition to acting through AMPARs, AA3 also acts as a non-competitive NMDA receptor (NMDAR) modulator with a neuroprotective capacity against ischemic brain injury and overexcitation in rats. These findings collectively suggest that AA3 possesses a unique ability to modulate the functions of both AMPARs and NMDARs. Concordantly, behavioral studies indicate that AA3 not only facilitates hippocampal long-term potentiation but also enhances spatial reference memory formation in mice. These multifaceted roles suggest that AA3 is an attractive candidate for further development as a cognitive enhancer capable of alleviating memory dysfunctions associated with aging and neurodegenerative diseases.
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China [4] HKUST-Jinan Joint Laboratory of Innovative Drug Discovery, Jinan University, Guangzhou, China.
authors: Fanny C F
authors: FC
authors: Ip
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Wing-Yu
authors: WY
authors: Fu
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Elaine Y L
authors: EY
authors: Cheng
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Estella P S
authors: EP
authors: Tong
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Ka-Chun
authors: KC
authors: Lok
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Yan
authors: Y
authors: Liang
authors: 1] HKUST-Jinan Joint Laboratory of Innovative Drug Discovery, Jinan University, Guangzhou, China [2] Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China [3] Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, China.
authors: Wen-Cai
authors: WC
authors: Ye
authors: 1] Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China [3] State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China [4] HKUST-Jinan Joint Laboratory of Innovative Drug Discovery, Jinan University, Guangzhou, China.
authors: Nancy Y
authors: NY
authors: Ip
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D065854:Spatial Navigation / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D012503:Saponins; D014315:Triterpenes; C473640:anemoside A3; D016202:N-Methylaspartate
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