scholarly journals Cynomorium songaricum Extract Alleviates Memory Impairment through Increasing CREB/BDNF via Suppression of p38MAPK/ERK Pathway in Ovariectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Fang-ze Tian ◽  
Hong-sheng Chang ◽  
Jian-xun Liu ◽  
Junchao Zheng ◽  
Dan Cheng ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Learning And Memory ◽  
Protein Kinases ◽  
Sham Group ◽  
Pyramidal Neurons ◽  
Mitogen Activated Protein Kinase ◽  
Ovariectomized Rats ◽  
Estradiol Valerate ◽  
Hippocampal Ca1 ◽  
Extracellular Regulated Protein Kinases

Cynomorium songaricum Rupr is a very important traditional Chinese medicine for tonifying the kidney, which has a significant effect on improving estrogen level on the long term. In many studies, it can improve the learning and memory function of ovariectomized (OVX) model animals. 10 of the 50 rats received only bilateral back surgery and were harvested with the same amount of fat as the ovaries without removing the ovaries as sham group; remains underwent bilateral ovariectomy and equally randomized into five groups: sham group, with OVX as model group, estradiol valerate (EV, 0.2 mg/kg) as positive control, with 3.3 and 33 mg/kg body weight/day of ethyl acetate extract of Cynomorium songaricum extract (CSE) as low and high dosage groups, respectively. The orally administered CSE to ovariectomized rats exerted an ameliorative effect on learning and memory in the Morris water maze tests. All rats were sacrificed after 8 weeks of treatment, and tissue was analyzed using histopathology and electron microscopy. To comprehensively examine the mechanism, brain derived neurotrophic factor (BDNF), p-p38 mitogen-activated protein kinase (p-p38MAPK), extracellular regulated protein kinases (ERK), p-extracellular regulated protein kinases (p-ERK), and p-cAMP-response element binding protein (p-CREB) were detected by Western blotting. Using histopathology and electron microscopy, it was clearly observed that the pyramidal neurons of the hippocampal CA1 area were reduced in the OVX groups, indicating that CSE could attenuate the loss of pyramidal neurons in hippocampal CA1 and revert the synaptic morphological variations produced by ovariectomy. Mechanistically, the expressions of p-p38MAPK and p-ERK levels were significantly downregulated by CSE intervention, whereas the BDNF and p-CREB were significantly upregulated by CSE as compared to the control. Concisely, Cynomorium songaricum Rupr exhibited potential therapeutic effect on Neuroprotection of ovariectomized rats, and its effect was possibly exerted by p-CREB/BDNF mediated down regulation of ERK/p38MAPK.

Plastic changes in dendritic spines of hippocampal CA1 pyramidal neurons from ovariectomized rats after estradiol treatment

2012 ◽  
Vol 1470 ◽  
pp. 1-10 ◽  
Author(s):  
Dulce A. Velázquez-Zamora ◽  
David González-Tapia ◽  
Myrna M. González-Ramírez ◽  
Mario E. Flores-Soto ◽  
Eduardo Vázquez-Valls ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Ovariectomized Rats ◽  
Estradiol Treatment ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Plastic Changes

scholarly journals Xiao-Yao-San Formula Improves Cognitive Ability by Protecting the Hippocampal Neurons in Ovariectomized Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lina Liu ◽  
Fei Ge ◽  
Haoran Yang ◽  
Huilian Shi ◽  
Weiting Lu ◽  
...  
Keyword(s):  
Western Blot ◽  
Learning And Memory ◽  
Cognitive Abilities ◽  
Hippocampal Neurons ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
High Dose ◽  
Pi3k Signaling ◽  
Hippocampal Ca1 ◽  
Golgi Staining

Xiao-Yao-San (XYS) decoction is a traditional Chinese medicine formula. This study aimed to investigate the effect of XYS on cognitive abilities and its underlying mechanism in ovariectomized rats. Female Sprague-Dawley rats were ovariectomized and treated with XYS (3 g/kg or 9 g/kg) by gavage, with subcutaneous injection of 17-β estradiol (E2, 2 μg/kg) as a positive drug control and gavage of 1 ml saline (0.9%) as a placebo control. After 6 weeks of treatment, rats were examined using the Morris water maze test. The estradiol level in the serum and hippocampus was measured by ELISA. Golgi staining was performed to observe neuronal morphology in the hippocampus. Apoptosis of hippocampal cells was observed by TUNEL staining. The protein content of N-methyl-D-aspartate receptor (NMDAR) 2A and 2B in the hippocampal CA1 region was determined by Western blot and immunohistochemistry. Expression of estrogen receptor (ER) and PI3K signaling was detected by Western blot. Compared with the sham group, both learning and memory were impaired in ovariectomized rats. Rats treated with E2 or high-dose XYS showed better learning and memory compared with the saline-treated rats. High-dose XYS significantly reduced escape latency in the spatial acquisition trial; meanwhile, the cross times and duration in the probe quadrant were increased in the spatial probe trial. High-dose XYS promoted the de novo synthesis of E2 content in the hippocampus but had no significant effect on the serum E2 level. Golgi staining indicated that high-dose XYS could increase the branch number and density of dendritic spines in the hippocampal CA1 area. TUNEL staining showed that high-dose XYS alleviated ovariectomy-induced neuronal apoptosis. The expression level of NMDAR2A and NMDAR2B in hippocampal CA1 was upregulated by XYS treatment. The beneficial effect of XYS was through activating ERα-PI3K signaling. In conclusion, high-dose XYS treatment can improve the cognitive abilities of ovariectomized rats by protecting the hippocampal neurons and restoring the hippocampal E2 level.

scholarly journals Chemerin Promotes Mitogen-activated Protein Kinase / Extracellular Regulated Protein Kinases Activation to Induce Inflammatory Factor Production in Rat Synoviocytes

2021 ◽  
Author(s):  
chen wang ◽  
Songrui Zhang ◽  
Longao Huang ◽  
Jianyi Liu ◽  
Gang Du ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Protein Kinases ◽  
Synovial Tissue ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Mitogen Activated Protein ◽  
Extracellular Regulated Protein Kinases

Abstract AimChemerin is a chemokine from adipose tissue that specifically binds to the G protein-coupled receptor ChemR23 and has a chemotactic effect on macrophages and dendritic cells. A correlation between chemerin levels in synovial fluid and disease severity has been demonstrated in patients with osteoarthritis. However, the specific mechanism by which chemerin exerts its effects on osteoarthritis remains unclear. In this study, we investigated the mechanism of chemerin-associated synoviocyte inflammation.MethodsCell Counting Kit-8 (CCK-8) assays were used to identify concentrations of chemerin that had an effect on normal rat synoviocytes. The expression changes of mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) pathway marker genes, including MEK, ERK, matrix metalloproteinase (MMP)-3 and MMP-13, were detected by fluorescence quantitative polymerase chain reaction (PCR). The phosphorylation of MEK, ERK1/2 and p38 mitogen-activated protein kinases (p38MAPK) by chemerin was analyzed by Western blotting, and the production of inflammatory factors after chemerin treatment was determined by enzyme-linked immunosorbent assay (ELISA). For in vivo assessment of chemerin function, rats were subjected to knee operation to provide a model for arthritis. The knees were then injected with normal saline or recombinant chemerin, and three weeks later, the synovium and knee joint tissue were harvested for HE staining observation and the synovial tissue was harvested for ELISA.ResultsChemerin was demonstrated to enhance the proliferation of synoviocytes in a dose-dependent manner. The stimulatory effect of chemerin on synoviocytes was shown to involve the activation of MEK, ERK1/2 and p38, which was associated with the production of MMP-13, MMP-3, interleukin (IL)-6 and IL-1β by synoviocytes. Inhibition of the ERK1/2 signaling pathway significantly inhibited chemerin-induced MMP-13, MMP-3, IL-6 and IL-1β production. HE staining showed that the degree of synovial hyperplasia and articular cartilage abrasion was more severe in chemerin-treated rats after knee operation. The articular cartilage surface was damaged, and the synovial tissue showed inflammatory cell infiltration. In rats that underwent operation without chemerin treatment, there was a slight inflammatory infiltration and higher levels of inflammatory factors as compared to unoperated rats; however, secretion of the downstream inflammatory factors IL-6, matrix metalloproteinases (MMP-3 and MMP-13) and IL-1β was significantly greater in the drug-treated group (P<0.05).ConclusionChemerin enhances the production of inflammatory factors in synoviocytes by activating the MEK/ERK signaling pathway.

scholarly journals Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol

2012 ◽  
Vol 70 (11) ◽  
pp. 874-879 ◽  
Author(s):  
Reihaneh Sadeghian ◽  
Masoud Fereidoni ◽  
Mohammad Soukhtanloo ◽  
Hamid Azizi-Malekabadi ◽  
Mahmoud Hosseini
Keyword(s):  
Nitric Oxide ◽  
Learning And Memory ◽  
Memory Deficits ◽  
Ovariectomized Rats ◽  
Estradiol Valerate ◽  
High Dose ◽  
Trial Test ◽  
Learning And Memory Deficits ◽  
Underlying Mechanisms ◽  
Nitric Oxide Metabolites

The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001). The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1) than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively). Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001). These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.

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