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 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 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 Annona atemoya Leaf Extract Improves Scopolamine-Induced Memory Impairment by Preventing Hippocampal Cholinergic Dysfunction and Neuronal Cell Death

2019 ◽  
Vol 20 (14) ◽  
pp. 3538 ◽  
Author(s):  
Eunjin Sohn ◽  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Passive Avoidance ◽  
Memory Impairment ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acetylcholinesterase Activity ◽  
Hippocampal Neurogenesis ◽  
Avoidance Task ◽  
Y Maze

We explored the preventative effect of Annona atemoya leaf (AAL) extract on memory impairment in a scopolamine (SCO)-induced cognitive deficit mouse model. Fifty-eight mice were randomly divided into six groups and orally treated with AAL extract at (50, 100, or 200 mg/kg) or tacrine (TAC) for 21 days. Memory deficits were induced by a single injection of 1 mg/kg SCO (i.p.) and memory improvement was evaluated by using behavioral tests such as the passive avoidance task and Y-maze test. The levels of cholinergic functions, neuronal cell death, reactive oxygen species, and protein expression related to hippocampal neurogenesis were examined by immunohistochemical staining and western blotting. The administration of AAL extract improved memory impairment according to increased spontaneous alternation in the Y-maze and step-through latency in passive avoidance test. AAL extract treatment increased the acetylcholine content, choline acetyltransferase, and acetylcholinesterase activity in the hippocampus of SCO-stimulated mice. In addition, AAL extract attenuated oxidative stress-induced neuronal cell death of hippocampal tissue. In terms of the regulatory mechanisms, AAL extract treatment reversed the SCO-induced decreases in the expression of Akt, phosphorylation of cAMP response element binding protein, and brain-derived neurotrophic factor. Our findings demonstrate that AAL extract has the ability to alleviate memory impairment through preventative effect on cholinergic system dysfunction and oxidative stress-related neuronal cell death in a SCO-induced memory deficit animal model. Overall, AAL may be a promising plant resource for the managing memory dysfunction due to neurodegenerative diseases, such as Alzheimer’s disease (AD).

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 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.

scholarly journals Standardized Extract (HemoHIM) Protects against Scopolamine-Induced Amnesia in a Murine Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Seul-Ki Kim ◽  
Da-Ae Kwon ◽  
Yong Sang Kim ◽  
Hak Sung Lee ◽  
Hyun Kyu Kim ◽  
...  
Keyword(s):  
Murine Model ◽  
Memory Impairment ◽  
Therapeutic Potential ◽  
Muscarinic Acetylcholine Receptor ◽  
Camp Response Element Binding ◽  
Avoidance Task ◽  
Mrna Levels ◽  
Object Recognition Test ◽  
Y Maze ◽  
Element Binding Protein

HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) designed for immune regulation. In the present study, the memory-enhancing effects of a standardized extract (HemoHIM) on scopolamine-induced memory impairment in a murine model was investigated. To induce amnesia, scopolamine (1 mg/kg) was intraperitoneally (i.p.) injected into mice 30 min before the start of behavioral tests. The Y-maze, novel object recognition test (NORT), and passive avoidance task (PAT) were used to evoke memory functions. HemoHIM significantly improved scopolamine-induced memory impairment in ICR mice, which was evidenced by an improvement of spontaneous alternation in the Y-maze, recognition index in NORT, and latency time in PAT. To elucidate the possible mechanism, the cholinergic activity and mRNA levels of choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) were measured using reverse transcription (RT-PCR) and western blot analyses, respectively. HemoHIM treatment attenuated the scopolamine-induced hyperactivation of acetylcholinesterase (AchE) activity. In addition, ChAT, mAchR, and CREB mRNA levels were increased in the hippocampus compared with the scopolamine group. Furthermore, HemoHIM treatment resulted in elevated BDNF protein expression. These results indicate that HemoHIM may exert antiamnesic activity by increasing Ach and inhibiting AchE in the hippocampus. In addition, HemoHIM has therapeutic potential by upregulating ChAT, mAchR, and BDNF, which is apparently mediated by activation of the CREB and ERK signaling pathways.

scholarly journals Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment via CREB-BDNF Signalling

2020 ◽  
Vol 21 (23) ◽  
pp. 8994
Author(s):  
Matteo Spinelli ◽  
Francesca Natale ◽  
Marco Rinaudo ◽  
Lucia Leone ◽  
Daniele Mezzogori ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Memory Impairment ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Camp Response Element Binding ◽  
Regulatory Sequences ◽  
Camp Response Element ◽  
Creb Phosphorylation ◽  
Element Binding Protein

Overnutrition and metabolic disorders impair cognitive functions through molecular mechanisms still poorly understood. In mice fed with a high fat diet (HFD) we analysed the expression of synaptic plasticity-related genes and the activation of cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signalling. We found that a HFD inhibited both CREB phosphorylation and the expression of a set of CREB target genes in the hippocampus. The intranasal administration of neural stem cell (NSC)-derived exosomes (exo-NSC) epigenetically restored the transcription of Bdnf, nNOS, Sirt1, Egr3, and RelA genes by inducing the recruitment of CREB on their regulatory sequences. Finally, exo-NSC administration rescued both BDNF signalling and memory in HFD mice. Collectively, our findings highlight novel mechanisms underlying HFD-related memory impairment and provide evidence of the potential therapeutic effect of exo-NSC against metabolic disease-related cognitive decline.

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