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 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.

scholarly journals Effects of a Nutritional Formulation Containing Caprylic and Capric Acid, Phosphatidylserine, and Docosahexaenoic Acid in Streptozotocin-Lesioned Rats

2020 ◽  
Vol 4 (1) ◽  
pp. 353-363
Author(s):  
Eric L.R. Moura ◽  
Hellin dos Santos ◽  
Ana Paula M. Celes ◽  
Taysa B. Bassani ◽  
Leonardo C. Souza ◽  
...  
Keyword(s):  
Object Recognition ◽  
Recognition Test ◽  
Memory Impairment ◽  
Saline Solution ◽  
Capric Acid ◽  
Test Results ◽  
Object Recognition Test ◽  
Y Maze ◽  
Post Hoc ◽  
Medical Nutrition

Background: It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and progression. Some studies on rodents using intraventricular streptozotocin (STZ) injection showed that this toxin changes cerebral glucose metabolism and insulin signaling pathways. Objective: The aim of the present study was to evaluate whether a nutritional formulation could reduce cognitive impairment in STZ-induced animals. Methods: The rats were randomly divided into two groups: sham and STZ. The STZ group received a single bilateral STZ-ICV injection (1 mg/kg). The sham group received a bilateral ICV injection of 0.9% saline solution. The animals were treated with AZ1 formulation (Instanth® NEO, Prodiet Medical Nutrition) (1 g/kg, PO) or its vehicle (saline solution) for 30 days, once a day starting one day after the stereotaxic surgery (n = 6–10). The rats were evaluated using the open field test to evaluate locomotor activity at day 27 after surgery. Cognitive performance was evaluated at day 28 using the object recognition test and the spatial version of the Y-maze test. At day 30, the rats were anesthetized with chloral hydrate (400 mg/kg, i.p) and euthanized in order to evaluate IBA1 in the hippocampus. The differences were analyzed using one-way ANOVA with Bonferroni’s or Kruskal Wallis with Dunn’s post-hoc test. Results/Conclusion: STZ-lesioned rats present memory impairment besides the increased microglial activation. The treatment with AZ1 formulation reversed the memory impairment observed in the object recognition test and Y-maze and also reduced IBA1 in CA1 and DG.

scholarly journals Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 888 ◽  
Author(s):  
Rafiad Islam ◽  
Kentaro Matsuzaki ◽  
Eri Sumiyoshi ◽  
Md Emon Hossain ◽  
Michio Hashimoto ◽  
...  
Keyword(s):  
Working Memory ◽  
Camp Response Element Binding ◽  
Normal Diet ◽  
Learning Ability ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Object Recognition Test ◽  
Male Wistar Rats ◽  
Neurotropic Factor ◽  
Bdnf Pathway

Theobromine (TB) is a primary methylxanthine found in cacao beans. cAMP-response element-binding protein (CREB) is a transcription factor, which is involved in different brain processes that bring about cellular changes in response to discrete sets of instructions, including the induction of brain-derived neurotropic factor (BDNF). Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been strongly implicated in the memory formation of different species as a key regulator of gene expression. Here we investigated whether TB acts on the CaMKII/CREB/BDNF pathway in a way that might improve the cognitive and learning function in rats. Male Wistar rats (5 weeks old) were divided into two groups. For 73 days, the control rats (CN rats) were fed a normal diet, while the TB-fed rats (TB rats) received the same food, but with a 0.05% TB supplement. To assess the effects of TB on cognitive and learning ability in rats: The radial arm maze task, novel object recognition test, and Y-maze test were used. Then, the brain was removed and the medial prefrontal cortex (mPFC) was isolated for Western Blot, real-time PCR and enzyme-linked immunosorbent assay. Phosphorylated CaMKII (p-CaMKII), phosphorylated CREB (p-CREB), and BDNF level in the mPFC were measured. In all the behavior tests, working memory seemed to be improved by TB ingestion. In addition, p-CaMKII and p-CREB levels were significantly elevated in the mPFC of TB rats in comparison to those of CN rats. We also found that cortical BDNF protein and mRNA levels in TB rats were significantly greater than those in CN rats. These results suggest that orally supplemented TB upregulates the CaMKII/CREB/BDNF pathway in the mPFC, which may then improve working memory in rats.

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 Antidepressant and Anxiolytic-Like Effects of the Stem Bark Extract of Fraxinus rhynchophylla Hance and Its Components in a Mouse Model of Depressive-Like Disorder Induced by Reserpine Administration

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Ri Kim ◽  
Bo-Kyung Park ◽  
Chang-Seob Seo ◽  
No Soo Kim ◽  
Mi Young Lee
Keyword(s):  
Mouse Model ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Stress Hormones ◽  
Stem Bark ◽  
Plasma Corticosterone ◽  
Camp Response Element Binding ◽  
Bark Extract ◽  
Mrna Levels ◽  
Behavioral Experiments ◽  
Element Binding Protein

There is an urgent need to find antidepressants that can be administered for long periods without inducing severe side effects to replace conventional antidepressants that control monoamine levels, such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRI). We sought to determine the antidepressant effects of Fraxinus rhynchophylla Hance (F. rhynchophylla Hance, FX) and its components on a reserpine-induced mouse model. One hour after oral administration of FX (30, 50, and 100 mg/kg), esculin (50 mg/kg), esculetin (50 mg/kg), fraxin (50 mg/kg), and fluoxetine (20 mg/kg), reserpine was delivered intraperitoneally to mice. Behavioral experiments were conducted to measure anxiety and depressive-like behaviors after 10 days of administration. FX and its components increased the number of entries into the center of an open field as well as distance traveled within it and decreased immobility duration in the forced swim and tail suspension tests. Reserpine-induced increases in plasma corticosterone concentrations were attenuated by the administration of FX and its components, which were also found to decrease the reserpine-induced enhancement of mRNA levels of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor (TNF)-α, pro-inflammatory cytokines. Finally, the diminished expressions of hippocampal phosphorylated cAMP response element-binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) by reserpine were increased by FX and its components. Our results suggest that FX and its components regulate anxiety and depressive-like behaviors through stress hormones, immune regulation, and the activation of neuroprotective mechanisms, further supporting the potential of FX and its components as antidepressants.

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).

Amitriptyline and phenytoin prevents memory deficit in sciatic nerve ligation model of neuropathic pain

2016 ◽  
Vol 27 (2) ◽  
Author(s):  
Wahab Imam Abdulmajeed ◽  
Ridwan Babatunde Ibrahim ◽  
Azeez Olakunle Ishola ◽  
Wasiu Gbolahan Balogun ◽  
Ansa Emmanuel Cobham ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Memory Impairment ◽  
Wistar Rats ◽  
Memory Deficit ◽  
Neural Population ◽  
Sham Control ◽  
Object Recognition Test ◽  
Y Maze ◽  
Prefrontal Cortices

AbstractPhenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain.Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both ‘Y’ maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin.There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the ‘Y’ maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals.The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.

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 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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