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 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.

scholarly journals Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the α5 Subunit of the GABAAReceptor

2002 ◽  
Vol 22 (13) ◽  
pp. 5572-5580 ◽  
Author(s):  
Neil Collinson ◽  
Frederick M. Kuenzi ◽  
Wolfgang Jarolimek ◽  
Karen A. Maubach ◽  
Rosa Cothliff ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Learning And Memory ◽  
Enhanced Learning ◽  
Gabaergic Synaptic Transmission

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.

scholarly journals Hippocampal Knockout of p300 Affects Learning and Memory in Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1044-1044
Author(s):  
Chase Rector ◽  
Lin Wang
Keyword(s):  
Learning And Memory ◽  
Cognitive Flexibility ◽  
Negative Impact ◽  
Test Results ◽  
Behavioral Tests ◽  
Object Recognition Test ◽  
Learning Skills ◽  
Maze Test ◽  
New Information ◽  
Lysine Acetyltransferase

Abstract Aging has been associated with cognitive decline, as seen in various learning and memory processes. Specifically, p300, a lysine acetyltransferase, has been shown to decrease with age, which could have an effect on cognition. In a series of behavioral tests, the effect of the knockout of p300 was studied in mice. In the water T maze test and the object recognition test, the results conveyed that the mice’s learning skills had not been impacted by the knockout of p300. But the water T maze test results further showed that the p300 knockout mice had a decline in their cognitive flexibility to new information. These findings suggest that the knockout of p300 has a negative impact on cognition. We expect that the overexpression of p300 in older mice will restore the cognition that might have been lost with aging.

scholarly journals Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: a challenge against conventional interpretation of the test

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hirotaka Shoji ◽  
Tsuyoshi Miyakawa
Keyword(s):  
Elevated Plus Maze ◽  
Plasma Corticosterone ◽  
Illumination Level ◽  
Test Battery ◽  
Lower Percentage ◽  
Behavioral Tests ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Corticosterone Response

AbstractThe elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear. In this study, we investigated the effects of experience with a battery of behavioral tests, the wall color of the closed arms, and illumination level on the behavior and plasma corticosterone responses in the elevated plus maze in male C57BL/6J mice. Mice were either subjected to a series of behavioral tests, including assessments of general health and neurological function, a light/dark transition test, and an open field test, or left undisturbed until the start of the elevated plus maze test. The mice with and without test battery experience were allowed to freely explore the elevated plus maze. The other two independent groups of naïve mice were tested in mazes with closed arms with different wall colors (clear, transparent blue, white, and black) or different illumination levels (5, 100, and 800 lx). Immediately after the test, blood was collected to measure plasma corticosterone concentrations. Mice with test battery experience showed a lower percentage of open arm time and entries and, somewhat paradoxically, had lower plasma corticosterone levels than the mice with no test battery experience. Mice tested in the maze with closed arms with clear walls exhibited higher open arm exploration than mice tested in the maze with closed arms with black walls, while there were no significant differences in plasma corticosterone levels between the different wall color conditions. Illumination levels had no significant effects on any measure. Our results indicate that experience with other behavioral tests and different physical features of the maze affect elevated plus maze behaviors. Increased open arm time and entries are conventionally interpreted as decreased anxiety-like behavior, while other possible interpretations are considered: open arm exploration may reflect heightened anxiety and panic-like reaction to a novel situation under certain conditions. With the possibility of different interpretations, the present findings highlight the need to carefully consider the test conditions in designing experiments and drawing conclusions from the behavioral outcomes in the elevated plus maze test in C57BL/6J mice.

Possible role of mitochondria in posttetanic potentiation of GABAergic synaptic transmission in rat neocortical cell cultures

Synapse ◽  
2005 ◽  
Vol 58 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Maksim V. Storozhuk ◽  
Svetlana Y. Ivanova ◽  
Pavel M. Balaban ◽  
Platon G. Kostyuk
Keyword(s):  
Synaptic Transmission ◽  
Cell Cultures ◽  
Posttetanic Potentiation ◽  
Gabaergic Synaptic Transmission

Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy

2016 ◽  
Vol 86 ◽  
pp. 109-120 ◽  
Author(s):  
Marco Fuenzalida ◽  
Claudia Espinoza ◽  
Miguel Ángel Pérez ◽  
Cheril Tapia-Rojas ◽  
Loreto Cuitino ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Synaptic Transmission ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Inhibitory Synaptic Transmission

Protective Effects of Dendrobium nobile Lindl. Alkaloids on Alzheimer's Disease-like Symptoms Induced by High-methionine Diet

2021 ◽  
Vol 19 ◽  
Author(s):  
Tingting Pi ◽  
Guangping Lang ◽  
Bo Liu ◽  
Jingshan Shi
Keyword(s):  
Alzheimer’S Disease ◽  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Cpg Island ◽  
Morris Water Maze Test ◽  
Dendrobium Nobile ◽  
Maze Test ◽  
Neuron Damage ◽  
Cpg Island Methylation

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) had potential benefits for AD. Object: Whether DNLA can improve AD-like symptoms induced by HMD is to be explored. Method: Mice were fed with 2% HMD diet for 11 weeks, the DNLA20 control group (20 mg/kg), DNLA10 group (10 mg/kg), and DNLA20 group (20 mg/kg) were administrated with DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl stainings. Levels of homocysteine (Hcy), beta-amyloid 1-42 (Aβ1-42), S-adenosine methionine (SAM), and S-adenosine homocysteine (SAH) were detected by ELISA. Immunofluorescence and western blotting (WB) were used to determine the expression of proteins. CPG island methylation. Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence stainings showed that DNLA alleviated neuron damage and reduced the 5-methylcytosine (5-mC), Aβ1-40, and Aβ1-42 levels. DNLA also decreased the levels of Hcy and Aβ1-42 in the serum, along with decreased SAM/SAH levels in the liver tissue. WB results showed that DNLA down-regulated the expression of the amyloid-precursor protein (APP), presenilin-1 (PS1), beta-secretase-1 (BACE1), DNA methyltransferase1 (DNMT1), Aβ1-40, and Aβ1-42 proteins. DNLA also up-regulated the expression of the protein of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a, and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes. Conclusions: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.

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