title: Notoginsenoside R1 increases neuronal excitability and ameliorates synaptic and memory dysfunction following amyloid elevation.
abstract: Neurodegeneration and synaptic dysfunction observed in Alzheimer's disease (AD) have been associated with progressive decrease in neuronal activity. Here, we investigated the effects of Notoginsenoside R1 (NTR1), a major saponin isolated from Panax notoginseng, on neuronal excitability and assessed the beneficial effects of NTR1 on synaptic and memory deficits under the Aβ-enriched conditions in vivo and in vitro. We assessed the effects of NTR1 on neuronal excitability, membrane ion channel activity, and synaptic plasticity in acute hippocampal slices by combining electrophysiological extracellular and intracellular recording techniques. We found that NTR1 increased the membrane excitability of CA1 pyramidal neurons in hippocampal slices by lowering the spike threshold possibly through a mechanism involving in the inhibition of voltage-gated K(+) currents. In addition, NTR1 reversed Aβ1-42 oligomers-induced impairments in long term potentiation (LTP). Reducing spontaneous firing activity with 10 nM tetrodotoxin (TTX) abolished the protective effect of NTR1 against Aβ-induced LTP impairment. Finally, oral administration of NTR1 improved the learning performance of the APP/PS1 mouse model of AD. Our work reveals a novel mechanism involving in modulation of cell strength, which contributes to the protective effects of NTR1 against Aβ neurotoxicity.
authors.affiliation: 1] State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China [2] Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, Columbia University, New York, NY10032, USA [3].
authors.forename: Shijun
authors.initials: S
authors.lastname: Yan
authors.affiliation: 1] State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China [2] Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100088, China [3] Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100088, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China [2] Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100088, China [3] Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100088, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, Columbia University, New York, NY10032, USA.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.affiliation: 1] State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China [2] Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100088, China [3] Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100088, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D013779:Tetrodotoxin; D011188:Potassium; C072936:notoginsenoside R1