Hydrolase-Treated Royal Jelly Attenuates H2O2- and Glutamate-Induced SH-SY5Y Cell Damage and Promotes Cognitive Enhancement in a Rat Model of Vascular Dementia

Vascular dementia (VaD) is the second most common type of dementia following Alzheimer’s disease, but the therapeutic efficacy is still not effective. This makes the searching for novel neuroprotective agents important. Therefore, we hypothesized that royal jelly, a well-known traditional medicine, could attenuate memory impairment and brain damage in vascular dementia. This study determined the effects of royal jelly hydrolysate (RJH) and possible mechanism of cell damage and cognitive-enhancing effect in animal study. An in vitro study assessed the effects of RJH on acetylcholinesterase inhibitor, cell viability, and cell damage in SH-SY5Y neuroblastoma cells. Then, an in vivo study examined vascular dementia by the occlusion of the right middle cerebral artery (Rt.MCAO); adult male Wistar rats had been orally given RJH at doses ranging from 10, 50, to 100 mg/kg for 14 days before and 14 days after the occlusion of Rt.MCAO to mimic the VaD condition. Rats’ spatial memory was evaluated using Morris water maze and radial arm maze every 7 days after Rt.MCAO throughout a 14-day experimental period, and then, they were sacrificed and the acetylcholinesterase (AChE) activity in the hippocampus was determined. The results showed that RJH has no cytotoxic effect with the final concentration up to 500 μg protein/ml and reduces cell death from the H2O2- and glutamate-induced cell damage in in vitro neuroblastoma cells. Importantly, RJH significantly improved memory performance in Morris water maze test and radial arm maze and decreased the level of acetyl cholinesterase activity. In conclusion, RJH is the potential neuroprotective agent and cognitive enhancer for VaD.

Download Full-text

Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning

PLoS ONE ◽

10.1371/journal.pone.0191708 ◽

2018 ◽

Vol 13 (2) ◽

pp. e0191708 ◽

Cited By ~ 3

Author(s):

Akinori Higaki ◽

Masaki Mogi ◽

Jun Iwanami ◽

Li-Juan Min ◽

Hui-Yu Bai ◽

...

Keyword(s):

Deep Learning ◽

Mouse Model ◽

Vascular Dementia ◽

Morris Water Maze ◽

Water Maze ◽

Morris Water Maze Test ◽

Maze Test ◽

Predicting Outcome

Download Full-text

The Prophylactic and Therapeutic Effects of Fermented Cordyceps sinensis Powder, Cs-C-Q80, on Subcortical Ischemic Vascular Dementia in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/4362715 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10

Author(s):

Ying Chen ◽

Lifeng Fu ◽

Min Han ◽

Meiying Jin ◽

Jiaying Wu ◽

...

Keyword(s):

Object Recognition ◽

White Matter ◽

Vascular Dementia ◽

Morris Water Maze ◽

Water Maze ◽

Interleukin 1 ◽

Cordyceps Sinensis ◽

Morris Water Maze Test ◽

Therapeutic Effects ◽

Therapeutic Treatment

Corbrin Capsule, a preparation of Cordyceps sinensis analogue, is a pleiotropic traditional Chinese patent medicine with the main component of fermentative cordyceps fungus powder (Cs-C-Q80). The neuroprotective effects of Cs-C-Q80, as a substitution of Cordyceps sinensis, have not been fully identified. The objectives of this study were to explore the prophylactic and therapeutic effects of Cs-C-Q80 in vascular dementia mice model. The efficacy of Cs-C-Q80 was investigated in a molecular level as well. The subcortical ischemic vascular dementia was modelled by permanent right unilateral common carotid arteries occlusion (rUCCAO) in adult male mice. The animals were randomly divided and treated by gavage with vehicle (1% CMC-Na solution) (rUCCAO model) or Cs-C-Q80 powder at 0.2 g/kg or 1.0 g/kg, respectively. Preventive treatment was administrated by gavage daily for 7 days before rUCCAO, while therapeutic treatment was administrated continuously from 28 days after rUCCAO. Object recognition test and Morris water maze test were performed to evaluate the learning and working memory. The luxol fast blue stain (Kluver-Barrera method) and immunohistochemistry for myelin basic protein (MBP) were employed to determine the severity of white matter damage. Both preventive and therapeutic treatment with Cs-C-Q80 protected against the rUCCAO-induced memory impair in mice as determined by object recognition and Morris water maze tests. The histopathological analyses revealed significant white matter rarefaction and reduction of MBP expression in corpus callosum after rUCCAO, which could be counteracted by either preventive or therapeutic treatment with Cs-C-Q80. Moreover, the Cs-C-Q80 treatments inhibited rUCCAO-induced astrocytes activation and the tumor necrosis factor α (TNF-α) and interleukin-1β expression, indicating the anti-inflammatory roles of Cs-C-Q80 against subcortical ischemia. Cs-C-Q80 is a potential preparation for the prophylaxis and treatment of subcortical ischemic vascular dementia. The underlying pharmacological efficacy might be associated with suppression of myelin degeneration, glia activation, and inflammatory cytokines release.

Download Full-text

Abstract P233: Mas Receptor Deficiency Does Not Impair Cognitive Funcion of Vascular Dementia Model in the Presence of Angiotensin II Type 2 Receptor

Hypertension ◽

10.1161/hyp.70.suppl_1.p233 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Akinori Higaki ◽

Masaki Mogi ◽

Jun Iwanami ◽

Li-Juan Min ◽

Harumi Kan-no ◽

...

Keyword(s):

Vascular Dementia ◽

Morris Water Maze ◽

Knockout Mice ◽

Water Maze ◽

Morris Water Maze Test ◽

Mas Receptor ◽

Maze Test ◽

Y Maze ◽

Significant Difference

Objective: Angiotensin (Ang) converting enzyme (ACE) 2/ Ang-(1-7)/Mas receptor axis has been considered as protective arm in the renin-angiotensin system and Ang-(1-7) is thought to interact with Ang II type 2 (AT 2 ) receptor according. Mas receptor is expressed highly in hippocampus and blood vessels in brain, but its actual function is still unclear. Thus, we examined the possible roles of Mas receptor in relation to the vascular cognitive impairment focusing on the interaction with AT 2 receptor. Design and Methods: Male 10-week-old C57BL6 mice (wild-type, WT), Mas1 receptor knockout mice (MasKO) and AT 2 /Mas1 receptor double knockout mice (DKO) were subjected to bilateral carotid artery stenosis (BCAS) surgery. After six weeks from the treatment, we evaluated their cognitive function with Y-maze test and the Morris water maze test. Results: The cerebral blood flow (CBF) in each BCAS group was significantly reduced compared to its sham-operated counterparts (WT; 31.5±0.6 vs 28.0±0.8, MasKO; 31.7±0.8 vs 27.7±0.8, DKO; 33.0±0.5 vs 29.1±0.7). The alternation behavior (%) was significantly reduced in WT mice with BCAS compared to sham mice (69.6±3.5 vs 57.9±2.1), but there was no significant difference in MasKO and DKO mice (MasKO; 64.1±2.5 vs 63.1±2.5, DKO; 67.6±2.1 vs 61.1±4.0) in Y maze test. In the Morris water maze test, the mean arrival time at platform at day 5 (sec) was significantly higher in WT-BCAS mice than WT-sham mice (Sham; 20.9±4.6 vs BCAS; 47.3±6.5). In contrast to the results in WT, there was no significant difference in MasKO mice (Sham; 32.8±8.5 vs BCAS; 34.5±7.3). DKO-sham mice showed significantly lower spatial learning ability compared with WT-sham mice (DKO; 77.4±11.9 vs WT; 20.9±4.6). The total cell count in dentate gyrus area was significantly lower in WT-BCAS compared to WT-sham (sham; 255.7±7.0 vs BCAS; 209.4±5.4), but there was no significant change in MasKO mice(sham; 256.5±2.5 vs BCAS; 233.2±16.4). We could not see significant difference in the number of DCX-positive cells and the expressions of proinflammatory cytokines such as IL-6, TNF-α and MCP-1in all mouse groups. Conclusion: Mas receptor deficiency seems to be beneficial in vascular dementia on condition that AT 2 receptor exists.

Download Full-text

Effect of Nyctanthes arbor tristis leaf extract against scopolamine-induced cognitive impairment in rats

Herba Polonica ◽

10.1515/hepo-2015-0003 ◽

2015 ◽

Vol 60 (4) ◽

pp. 34-49

Author(s):

Bashetty Phanindhra ◽

Akondi Butchi Raju ◽

Gadiyaram Vikas ◽

Repala Anusha ◽

Donapati Deepika

Keyword(s):

Cognitive Impairment ◽

Protective Effect ◽

Morris Water Maze ◽

Water Maze ◽

Active Avoidance ◽

Ethanol Extract ◽

Thiobarbituric Acid ◽

Morris Water Maze Test ◽

Radial Arm Maze ◽

Maze Test

Summary Nyctanthes arbor tristis (NATE) ethanol extract (150 mg/kg, orally) was evaluated for its protective effect against scopolamine-induced (1 mg/kg i.p.) cognitive impairments in rats using behavioral models like radial arm maze test, Morris water maze test and active avoidance test. NATE effect was evaluated and compared with the standard piracetam (200mg/kg i.p.). NATE (p<0.005) significantly reversed the impairment produced by the scopolamine in radial arm maze test. In addition, NATE also decreased the time period taken to find the hidden platform in Morris water maze test and increased number of avoidances in active avoidance paradigm. Acetylcholinesterase activity and thiobarbituric acid levels were significantly (p<0.005) decreased along with the rise in activities of superoxide dismutase and catalase. This might suggest that the NATE has protective effect against scopolamine-induced cognitive impairment in rats through acetylcholine muscarinic receptor pathway and also antioxidant activity. No significant changes were found in histopathological studies of brain.

Download Full-text

Zhuyu Annao decoction promotes angiogenesis in mice with cerebral hemorrhage by inhibiting the activity of PHD3

Human & Experimental Toxicology ◽

10.1177/09603271211008523 ◽

2021 ◽

pp. 096032712110085

Author(s):

L Wu ◽

Y Hu ◽

L Jiang ◽

N Liang ◽

P Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Morris Water Maze ◽

Cerebral Hemorrhage ◽

Water Maze ◽

Luciferase Reporter ◽

Morris Water Maze Test ◽

Therapeutic Effects ◽

Vascular Endothelial ◽

Behavioral Experiments

Some traditional Chinese decoctions, such as Zhuyu Annao, exert favorable therapeutic effects on acute cerebral hemorrhage, hemorrhagic stroke, and other neurological diseases, but the underlying mechanism remains unclear. This study aimed to determine whether Zhuyu Annao decoction (ZYAND) protects the injured brain by promoting angiogenesis following intracerebral hemorrhage (ICH) and elucidate its specific mechanism. The effect of ZYAND on the nervous system of mice after ICH was explored through behavioral experiments, such as the Morris water maze and Rotarod tests, and its effects on oxidative stress were explored by detecting several oxidative stress markers, including malondialdehyde, nitric oxide, glutathione peroxidase, and superoxide dismutase. Real-time quantitative RT-PCR and WB were used to detect the effects of ZYAND on the levels of prolyl hydroxylase domain 3 (PHD3), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) in the brain tissues of mice. The effect of ZYAND on the NF-κB signaling pathway was detected using a luciferase reporter gene. A human umbilical cord vascular endothelial cell angiogenesis experiment was performed to determine whether ZYAND promotes angiogenesis. The Morris water maze test and other behavioral experiments verified that ZYAND improved the neurobehavior of mice after ICH. ZYAND activated the PHD3/HIF-1α signaling pathway, inhibiting the oxidative damage caused by ICH. In angiogenesis experiments, it was found that ZYAND promoted VEGF-induced angiogenesis by upregulating the expression of HIF-1α, and NF-κB signaling regulated the expression of HIF-1α by inhibiting PHD3. ZYAND exerts a reparative effect on brain tissue damaged after ICH through the NF-κB/ PHD3/HIF-1α/VEGF signaling axis.

Download Full-text

Protective effect of citicoline against aluminum-induced cognitive impairments in rats

Toxicology and Industrial Health ◽

10.1177/0748233716641869 ◽

2016 ◽

Vol 33 (4) ◽

pp. 308-317 ◽

Cited By ~ 9

Author(s):

Ahmed O Abdel-Zaher ◽

Mostafa M Hamdy ◽

Mahran S Abdel-Rahman ◽

Doaa H Abd El-hamid

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Passive Avoidance ◽

Morris Water Maze ◽

Cognitive Deficits ◽

Aluminum Chloride ◽

Water Maze ◽

Cognitive Impairments ◽

Radial Arm Maze ◽

Time Required

The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.

Download Full-text

Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer’s Disease

Neural Plasticity ◽

10.1155/2016/3131586 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Jing Jiang ◽

Gang Liu ◽

Suhua Shi ◽

Zhigang Li

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Frontal Lobe ◽

Morris Water Maze ◽

Water Maze ◽

Morris Water Maze Test ◽

Maze Test ◽

Model Of Alzheimer’S Disease ◽

Samp8 Mice

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer’s disease.Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer’s disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer’s disease (AD), and normal (N) groups were assessed.Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβamyloid content in the frontal lobe, compared with the AD group (P<0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD.Conclusion. MEA therapy may be superior to EA in treating Alzheimer’s disease as demonstrated in SAMP8 mice.

Download Full-text

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

Current Neuropharmacology ◽

10.2174/1570159x19666210809101945 ◽

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.

Download Full-text

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

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.411-414.3178 ◽

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.

Download Full-text