scholarly journals Stachys sieboldii Extract Supplementation Attenuates Memory Deficits by Modulating BDNF-CREB and Its Downstream Molecules, in Animal Models of Memory Impairment

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 917 ◽  
Author(s):  
Vijaya Ravichandran ◽  
Mina Kim ◽  
Seong Han ◽  
Youn Cha
Keyword(s):  
Memory Impairment ◽  
Neuronal Apoptosis ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Mechanism Study ◽  
Maze Test ◽  
Element Binding Protein ◽  
Inward Currents ◽  
Underlying Mechanisms ◽  
Stachys Sieboldii

Cholinergic dysfunction, impaired brain-derived neurotrophic factor and cAMP response element binding protein (BDNF-CREB) signaling are one of the major pathological hallmarks of cognitive impairment. Therefore, improving cholinergic neurotransmission, and regulating the BDNF-CREB pathway by downregulating apoptosis genes is one strategy for inhibiting the etiology of dementia. This study evaluates the potential effects of Stachys sieboldii MIQ (SS) extract against cognitive dysfunction and its underlying mechanisms. SS supplementation for 33 days improved scopolamine-induced memory impairment symptoms in Morris water maze test and Y-maze test. SS reduced the acetylcholineesterase activity and significantly increase acetylcholine and cholineacetyltransferase activity in the brain. In the subsequent mechanism study, SS regulated the mRNA expression level of neuronal plasticity molecules such as (nerve growth factor) NGF, BDNF, CREB, and its downstream molecules such as Bcl-2 and Egr-1 by downregulating the neuronal apoptosis targets in both hippocampus and frontal cortex. Additionally, inward currents caused by SS in hippocampal CA1 neurons was partially blocked by the GABA receptor antagonist picrotoxin (50 μM), suggesting that SS acts on synaptic/extrasynaptic GABAA receptors. These findings indicate that SS may function in a way that is similar to nootropic drugs by inhibiting cholinergic abnormalities, and neuronal apoptosis targets and ultimately increasing the expression of BDNF-CREB.

scholarly journals Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Ri Kim ◽  
Min Young Kwon ◽  
Malk Eun Pak ◽  
So Hyun Park ◽  
Jin Ung Baek ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Memory Impairment ◽  
Neuronal Cell ◽  
Acetylcholinesterase Activity ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Memory Impairments ◽  
Beneficial Effects ◽  
Element Binding Protein ◽  
Time Required

From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and mature brain-derived neurotrophic factor (mBDNF) expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments.

scholarly journals BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes

2020 ◽  
Vol 3 (9) ◽  
pp. e201900619
Author(s):  
Hyoung Kyu Kim ◽  
Tae Hee Ko ◽  
In-Sung Song ◽  
Yu Jeong Jeong ◽  
Hye Jin Heo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Therapeutic Potential ◽  
Cardiac Contractility ◽  
Camp Response Element Binding ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Calcium Calmodulin Dependent ◽  
Element Binding Protein ◽  
Underlying Mechanisms

Diabetic cardiomyopathy (DCM) is a major cause of mortality/morbidity in diabetes mellitus patients. Although tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous cardiovascular target, its effect on myocardial cells and mitochondria in DCM and the underlying mechanisms remain unknown. Here, we determined the involvement of BH4 deficiency in DCM and the therapeutic potential of BH4 supplementation in a rodent DCM model. We observed a decreased BH4:total biopterin ratio in heart and mitochondria accompanied by cardiac remodeling, lower cardiac contractility, and mitochondrial dysfunction. Prolonged BH4 supplementation improved cardiac function, corrected morphological abnormalities in cardiac muscle, and increased mitochondrial activity. Proteomics analysis revealed oxidative phosphorylation (OXPHOS) as the BH4-targeted biological pathway in diabetic hearts as well as BH4-mediated rescue of down-regulated peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) signaling as a key modulator of OXPHOS and mitochondrial biogenesis. Mechanistically, BH4 bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and activated downstream AMP-activated protein kinase/cAMP response element binding protein/PGC-1α signaling to rescue mitochondrial and cardiac dysfunction in DCM. These results suggest BH4 as a novel endogenous activator of CaMKK2.

Soybean Isoflavones Influences Learning and Memory and Caspase-3 Levels in the Hippocampus of Rats after MWM Test

2013 ◽  
Vol 411-414 ◽  
pp. 3178-3180
Author(s):  
Li Hai Jin ◽  
Xing Yu Zhao ◽  
Wei Zhang ◽  
Wei Chen ◽  
Guo Qing Sun ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Memory Impairment ◽  
Caspase 3 ◽  
Morris Water Maze Test ◽  
Once Daily ◽  
Soybean Isoflavones ◽  
Maze Test ◽  
Intermediate Dose

We assessed the effectiveness and mechanism of action of Soybean Isoflavones on learning and memory and Caspase-3 levels in the hippocampus of rats after Morris water maze (MWM test). Soybean Isoflavones (200,400 or 800 mg/kg/d) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of Soybean Isoflavones to increase learning and memory impairment. The levels of Caspase-3 in hippocampus of rats were detected by Westernblot after MWM test. Compared to untreated controls (P<0.01), MWM could be prolonged after Soybean Isoflavones treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" westernblot="" analysis="" showed="" that="" the="" protein="" expression="" of="" caspase-3="" was="" decreased="" in="" different="" concentration="" soybean="" isoflavones="" i="">P<0.05 and="" i="">P<0.01, respectively). The results suggest that Soybean Isoflavones is effective in improving the learning and memory in rats , the mechanism of which may be related Caspase ways.

scholarly journals Neuroprotective Effect and Molecular Mechanism of [6]-Gingerol against Scopolamine-Induced Amnesia in C57BL/6 Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Yul Kim ◽  
Yongtaek Seo ◽  
Chan Lee ◽  
Gyu Hwan Park ◽  
Jung-Hee Jang
Keyword(s):  
Escape Latency ◽  
Neuroprotective Effect ◽  
Camp Response Element Binding ◽  
Behavior Changes ◽  
Camp Response Element ◽  
Memory Impairments ◽  
Maze Test ◽  
Y Maze ◽  
Element Binding Protein ◽  
The Brain

We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day). To further verify the neuroprotective mechanism of GIN, we have focused on the brain-derived neurotrophic factor (BDNF). The administration of GIN elevated the protein expression of BDNF, which was mediated via the activation of protein kinase B/Akt- and cAMP-response element binding protein (CREB) signaling pathway. These results suggest that GIN may have preventive and/or therapeutic potentials in the management of memory deficit and cognitive impairment in mice with amnesia.

scholarly journals Effect of Evodia rutaecarpa (Juss) Benth extract on Alzheimer disease in mice

2020 ◽  
Vol 19 (4) ◽  
pp. 823-828
Author(s):  
Ang Cai ◽  
Liu Xiao ◽  
Yan-Ping Zhou ◽  
Zhi-Guo Zhang ◽  
Quan-Wei Yang
Keyword(s):  
Cognitive Function ◽  
Alzheimer Disease ◽  
Water Maze ◽  
Memory Impairment ◽  
Escape Latency ◽  
Memory Deficits ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Evodia Rutaecarpa ◽  
Mouse Hippocampus

Purpose: To investigate the protective effect of Evodia rutaecarpa (Juss.) Benth. extract (ERBE) against Alzheimer's disease in 3xTg-AD mice. Methods: The cognitive function of 3xTg-AD mice was assessed using Morris water maze test. The levels of amyloid beta deposits and NeuN in the mouse hippocampus were evaluated by immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were determined by western blot analysis. Results: ERBE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. The escape latency in the animals treated with 400 mg/kg ERBE (20.5 ± 1.3 s) was significantly higher than untreated 3xTg-AD mice (12.4 ± 1.3 s, p < 0.01). In addition, ERBE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expressions of BDNF (1.4 ± 0.2, p < 0.05) and TrkB (1.1 ± 0.2, p < 0.05) in 3xTg AD mice. Conclusion: The results suggest that ERBE administration may be a useful strategy for treating memory impairment induced by several neurodegenerative diseases. Keywords: Evodia rutaecarpa, Alzheimer, Memory impairment, NeuN-positive cells

scholarly journals Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc

2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Mingxian Shi ◽  
Jiafeng Ding ◽  
Lin Li ◽  
Hui Bai ◽  
Xinran Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Learning And Memory ◽  
Dose Group ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Memory Ability ◽  
Expression Levels ◽  
Element Binding Protein ◽  
High Level ◽  
Arc Gene

Ketamine has become a popular recreational drug due to its neuronal anesthesia effect and low price. The process of learning and memory is part of the distinctive high-level neural activities in animals. We investigated the effects of subanesthetic and anesthetic doses of ketamine on the learning and memory-related signal transduction mechanisms. We used the Morris water maze test to execute rats’ learning and memory ability and detected changes of Arc mRNA and Arc, cAMP-response element-binding protein (CREB), phospho-CREB (p-CREB), extracellular signal-regulated kinase (ERK), and phospho-ERK (p-ERK) protein expression in the hippocampus 10 min and 24 h after administration. Ten min after ketamine injection, the Arc gene and the protein expression levels increased in all groups; p-ERK only increased in the chronic subanesthetic dose group. After 24 h, the Arc gene and the protein expression levels of the subanesthetic dose group increased, but those of the chronic subanesthetic dose group and anesthetic dose group decreased. However, p-ERK increased in all groups. A chronic subanesthetic dose of ketamine could increase learning and memory ability through ERK, CREB, and Arc in a short time, and the high body temperature after the subanesthetic dose of ketamine injection was the main factor leading to changes in Arc. The subanesthetic dose of ketamine regulated learning and memory through ERK, CREB, and ARC 24 h after injection.

scholarly journals Xanthoceraside Ameliorates Mitochondrial Dysfunction Contributing to the Improvement of Learning and Memory Impairment in Mice with Intracerebroventricular Injection of Aβ1-42

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xue-Fei Ji ◽  
Tian-Yan Chi ◽  
Qian Xu ◽  
Xiao-Lu He ◽  
Xiao-Yu Zhou ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Learning And Memory ◽  
Memory Impairment ◽  
Mitochondrial Respiratory Chain ◽  
Morris Water Maze Test ◽  
Mice Model ◽  
Maze Test ◽  
Y Maze ◽  
Abnormal Increase ◽  
Improved Learning

The effects of xanthoceraside on learning and memory impairment were investigated and the possible mechanism associated with the protection of mitochondria was also preliminarily explored in Alzheimer’s disease (AD) mice model induced by intracerebroventricular (i.c.v.) injection of Aβ1-42. The results indicated that xanthoceraside (0.08–0.32 mg/kg) significantly improved learning and memory impairment in Morris water maze test and Y-maze test. Xanthoceraside significantly reversed the aberrant decrease of ATP levels and attenuated the abnormal increase of ROS levels both in the cerebral cortex and hippocampus in mice injected with Aβ1-42. Moreover, xanthoceraside dose dependently reversed the decrease of COX, PDHC, and KGDHC activity in isolated cerebral cortex mitochondria of the mice compared with Aβ1-42 injected model mice. In conclusion, xanthoceraside could improve learning and memory impairment, promote the function of mitochondria, decrease the production of ROS, and inhibit oxidative stress. The improvement effects on mitochondria may be through withstanding the damage of Aβto mitochondrial respiratory chain and the key enzymes in Kreb’s cycle. Therefore, the results from present study and previous study indicate that xanthoceraside could be a competitive candidate for the treatment of AD.

scholarly journals Memory-Enhancing Effects of Mangosteen Pericarp Water Extract through Antioxidative Neuroprotection and Anti-Apoptotic Action

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 34
Author(s):  
Yeonsoo Oh ◽  
Ha Thi Thu Do ◽  
Sunyoung Kim ◽  
Young-Mi Kim ◽  
Young-Won Chin ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Caspase 3 ◽  
Water Extract ◽  
Antioxidant Property ◽  
Morris Water Maze Test ◽  
Oxygen Species ◽  
Cortical Cells ◽  
Maze Test ◽  
Pharmacological Potential ◽  
Memory Enhancing

Mangosteen has long been utilized as a traditional medicine in Southeast Asia. Diverse extracts of mangosteen pericarp and its bioactive xanthones exhibit various bioactivities. However, the pharmacological potential of mangosteen pericarp water extract (MPW) has not been reported yet. This study used primary cultured rat cortical cells to investigate the effect of MPW on neurotoxicity. We found that MPW inhibited neurotoxicity and production of reactive oxygen species triggered by Aβ(25–35) or excitatory amino acids. MPW inhibited caspase 3 activation and DNA fragmentation in Aβ(25–35)- or N-methyl-D-aspartate-treated cells, suggesting an anti-apoptotic action. Additionally, MPW reduced lipid peroxidation and scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, assuring its antioxidant property. Furthermore, MPW suppressed β-secretase and acetylcholinesterase activities. These findings prompted us to evaluate its effect on memory dysfunction in scopolamine-treated mice using Morris water maze test. Oral administration of MPW at the dosage of 50, 100, or 300 mg/kg for four days significantly decreased the latency time to find the platform and markedly increased the swimming time in the target quadrant. Taken together, our results suggest that MPW exerts memory-enhancing effect through antioxidative neuroprotection and anti-apoptotic action. Accordingly, MPW may have a potential to prevent or treat memory impairment associated with Alzheimer’s disease.

scholarly journals Scrophularia buergeriana Extract (Brainon) Improves Scopolamine-Induced Neuronal Impairment and Cholinergic Dysfunction in Mice through CREB-BDNF Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 4286
Author(s):  
Hae-Jin Lee ◽  
Hae-Lim Kim ◽  
Dae-Young Lee ◽  
Dong-Ryung Lee ◽  
Bong-Keun Choi ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Avoidance Performance ◽  
Memory Loss ◽  
Adenosine Diphosphate ◽  
Acetylcholinesterase Activity ◽  
Camp Response Element Binding ◽  
Mrna Levels ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
Apoptotic Effects

We evaluated the effectiveness of Scrophularia buergeriana extract (Brainon) on cognitive dysfunction and determined its underlying mechanisms in a scopolamine (SCO)-treated mouse model of memory impairment. Brainon treatment for 28 days ameliorated the symptoms of memory impairment as indicated by the results of both passive avoidance performance and the Morris water mazes. Brainon lowered acetylcholinesterase activity and raised acetylcholine levels in the hippocampus. The treatment elevated the protein levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding (CREB). Additionally, the excessive generation of SCO-induced reactive oxygen species (ROS) and subsequent oxidative stress were suppressed by the enhancement of superoxide dismutase (SOD)-1 and SOD-2 proteins. mRNA levels of upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, as well as the apoptotic protein Bcl-2-associated X protein (Bax), cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase (PARP) expression after SCO injection were downregulated by Brainon treatment. Collectively, these findings suggested that Brainon possesses anti-amnesic effects through the CREB-BDNF pathway. Moreover, it exerted antioxidant, anti-inflammatory, and anti-apoptotic effects in SCO-induced mice exhibiting cognitive impairment and memory loss.

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