scholarly journals Astragaloside IV enhances memory and modulates hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice

2020 ◽  
Author(s):  
Fei Huang ◽  
Yunyi Lan ◽  
Jin Zhou ◽  
Liu Yang ◽  
Hao Guan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Signaling Pathway ◽  
Electrophysiological Recording ◽  
Inhibitory Synapses ◽  
Radial Arm Maze ◽  
Gabaergic Inhibition ◽  
Astragaloside Iv ◽  
Shuttle Box ◽  
Hippocampal Synaptic Plasticity ◽  
Maze Test

Abstract Background Astragaloside IV (ASIV) is one of the saponins isolated from Astragalus membranaceus, a widely used traditional Chinese medicine and a health product sold all over the world. However, so far, the effect of ASIV on GABAergic synaptic transmission has not been elucidated yet. In the present study, the effect of ASIV on memory and hippocampal synaptic plasticity was investigated in mice and down-regulated early growth response protein 1 (EGR-1) knockout mice. Methods Behavior tests including radial-arm maze test and shuttle-box test, liquid chromatography-tandem mass spectrometry, western blotting analysis, quantitative PCR, electrophysiological recording, and electron microscopy were used in this study. The difference of data was detected by unpaired student t-test or two-factor analysis of variance (ANOVA) or Mann-Whitney U test. Results ASIV was shown to enhance the learning and memory of mice in behavior tests, such as radial-arm maze test and shuttle-box test, as well as the synaptic plasticity in electrophysiological experiments. Moreover, it significantly reduced the concentration of gamma-aminobutyric acid (GABA) and the expression of glutamate decarboxylase 2 (GAD65) in mouse hippocampus, which was accompanied with decreased ratio of inhibitory synapses, and EGR-1, brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). When EGR-1 was knocked out, the promotive effects of ASIV on memory and synaptic plasticity, as well as the inhibitory effects on GAD65, BDNF and TrkB, were abolished. In addition, ASIV was found to down-regulate the pre-existing EGR-1 baseline to better adapt to the learning stimuli. Conclusions Together, these results demonstrated a novel role of ASIV in enhancing memory and modulating hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice.

Astragaloside IV suppressed hippocampal GABAergic synaptic transmission and enhanced memory through EGR-1 mediated BDNF/TrkB signaling pathway in mice

2020 ◽  
Author(s):  
Fei Huang ◽  
Weixuan Xue ◽  
Yunyi Lan ◽  
Yanlin Tao ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
Electrophysiological Recording ◽  
Radial Arm Maze ◽  
Behavioral Tests ◽  
Astragaloside Iv ◽  
Shuttle Box ◽  
Maze Test ◽  
Gabaergic Synaptic Transmission

Abstract Background: Astragaloside IV (ASIV) is one of the saponins isolated from Astragalus membranaceus, a widely used traditional Chinese medicine and a health product sold all over the world. However, so far, the effect of ASIV on GABAergic synaptic transmission has not been elucidated yet. In the present study, the effect of ASIV on memory and hippocampal GABAergic synaptic transmission was investigated in wild type and early growth response protein 1 (EGR-1) knockout mice. Methods: Behavioral tests including radial-arm maze test and shuttle-box test, liquid chromatography-tandem mass spectrometry, western blotting analysis, quantitative PCR, electrophysiological recording, and electron microscopy were used in this study. Results: ASIV was shown to enhance the learning and memory of mice in behavioral tests, such as radial-arm maze test and shuttle-box test. It significantly reduced the concentration of GABA, the expression of glutamate decarboxylase 2 (GAD65) as well as the ratio of inhibitory synapses in mouse hippocampus, which was accompanied with a suppression of hippocampal spontaneous inhibitory postsynaptic currents. ASIV administration decreased the expression of EGR-1, brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the hippocampus. Furthermore, blockage of BDNF/TrkB signaling with K-252a abrogated the effect of ASIV on GAD65 expression. When EGR-1 was knocked out, the promotive effects of ASIV on learning and memory, as well as the inhibitory effects on GABAergic synaptic transmission and GAD65, BDNF and TrkB expression, were abolished. In addition, ASIV was found to down-regulate the pre-existing EGR-1 baseline to better adapt to the learning stimuli. Conclusions: Together, these results demonstrated a novel role of ASIV in enhancing memory and reducing hippocampal GABAergic synaptic transmission through EGR-1 mediated BDNF/TrkB signaling pathway in mice.

scholarly journals Pharmacological modulation of AMPA receptor surface diffusion restores hippocampal synaptic plasticity and memory in Huntington’s disease

2018 ◽  
Author(s):  
Hongyu Zhang ◽  
Chunlei Zhang ◽  
Jean Vincent ◽  
Diana Zala ◽  
Caroline Benstaali ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Signaling Pathway ◽  
Surface Diffusion ◽  
Ampa Receptors ◽  
Molecular Basis ◽  
Super Resolution ◽  
Long Term Potentiation ◽  
Hippocampal Synaptic Plasticity

AbstractImpaired hippocampal synaptic plasticity is increasingly considered to play an important role in cognitive impairment in Huntington’s disease (HD). However, the molecular basis of synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that dysregulation of AMPA receptors (AMPARs) surface diffusion represents a molecular basis underlying the aberrant hippocampal synaptic plasticity during HD. AMPARs surface diffusion is increased in various HD neuronal models, which results in the failure of AMPARs surface stabilization after long-term potentiation (LTP) stimuli. This appears to result from a defective brain-derived neurotrophic factor (BDNF) - tyrosine receptor kinase B (TrkB) - Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling pathway that impacts the interaction between the AMPAR auxiliary subunit stargazin and postsynaptic density protein 95 (PSD-95). Notably, the disturbed AMPAR surface diffusion is rescued, via BDNF signaling pathway and by the antidepressant tianeptine. Tianeptine also restores the impaired LTP and hippocampus-dependent memory as well as anxiety/depression-like behavior in different HD mouse models. We thus unveil a mechanistic framework underlying hippocampal synaptic and memory dysfunction and propose a new perspective in HD treatment by targeting AMPAR surface diffusion.

scholarly journals Electroacupuncture Ameliorates Learning and Memory and Improves Synaptic Plasticity via Activation of the PKA/CREB Signaling Pathway in Cerebral Hypoperfusion

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Cai-Xia Zheng ◽  
Min Lu ◽  
Ya-Bi Guo ◽  
Feng-Xia Zhang ◽  
Hua Liu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Cerebral Hypoperfusion ◽  
Electrophysiological Recording ◽  
Learning And Memory Deficits ◽  
Creb Pathway

Electroacupuncture (EA) has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are ill-understood. The present study was undertaken to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following EA and to investigate the role of PKA/CREB pathway. We used a rat 2-vessel occlusion (2VO) model and delivered EA at Baihui (GV20) and Dazhui (GV14) acupoints. Morris water maze (MWM) task, electrophysiological recording, Golgi silver stain, Nissl stain, Western blot, and real-time PCR were employed. EA significantly (1) ameliorated the spatial learning and memory deficits, (2) alleviated long-term potentiation (LTP) impairment and the reduction of dendritic spine density, (3) suppressed the decline of phospho-CREB (pCREB) protein, brain-derived neurotrophic factor (BDNF) protein, and microRNA132 (miR132), and (4) reduced the increase of p250GAP protein of 2VO rats. These changes were partially blocked by a selective protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89), suggesting that the PKA/CREB pathway is potentially involved in the effects of EA. Moreover, any significant damage to the pyramidal cell layer of CA1 subregion was absent. These results demonstrated that EA could ameliorate learning and memory deficits and alleviate hippocampal synaptic plasticity impairment of cerebral hypoperfusion rats, potentially mediated by PKA/CREB signaling pathway.

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