scholarly journals Luteolin attenuates cognitive dysfunction induced by chronic cerebral hypoperfusion through the modulation of the PI3K/Akt pathway in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Haitao He ◽  
Xi Chen
Keyword(s):  
Cerebral Cortex ◽  
Object Recognition ◽  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Water Maze ◽  
Sham Group ◽  
Cerebral Hypoperfusion ◽  
Morris Water Maze Test ◽  
Model Group ◽  
Group I

Abstract Introduction In our study, we evaluated the beneficial effect of luteolin in the treatment of cognitive dysfunction in rat models induced by cerebral hypoperfusion by two-vessel occlusion (2-VO). Material and Methods Seventy-five male Sprague Dawley rats were subjected to 2-VO surgery, in all but 15 (the sham group, group I) the ligation being permanent to impair cognitive abilities. The sham group rats received saline instead of a drug; 15 2-VO rats were not injected at all (the model group, group II); 15 2-VO rats were administered luteolin at 50 mg/kg b.w. (the lut 50 group, group III); to a further 15 luteolin was given at 100 mg/kg b.w. (the lut 100 group, group IV); and the final 15 received nimodipine at 16 mg/kg b.w. as positive controls (the nimodipine group, group V). Object recognition and Morris water maze tests were performed to investigate memory ability. A Western blot test was also conducted to assess expression of phosphatidylinositol 3-kinase (PI3K), its downstream target protein kinase B (Akt), and the phosphorylated form (P-Akt) in cerebral cortex and hippocampus tissue samples. Results Significant variations in the discrimination index in the object recognition test, the escape latencies in the Morris water maze test, and expression levels of PI3K-p110α and PI3K-p85 were observed three months after 2-VO surgery in both lut groups, with a significant change in the nimodipine group compared to the model group. P-Akt and Akt were expressed significantly higher in both lut groups and the nimodipine group than in the model group. Conclusion Luteolin treatment of rats cognitively dysfunctional after experimental cerebral hypo perfusion was neuroprotective by activating the PI3K/Akt signals which inhibit neuronal death in the cerebral cortex and hippocampal region.

scholarly journals Improvement of Electroacupuncture on APP/PS1 Transgenic Mice in Spatial Learning and Memory Probably due to Expression of Aβand LRP1 in Hippocampus

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Wang ◽  
Yanhuan Miao ◽  
Jiawula Abulizi ◽  
Fu Li ◽  
Yuping Mo ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Normal Control ◽  
Water Maze ◽  
Normal Control Group ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Model Group ◽  
Amyloid A

Objectives. To explore the alterations ofβ-amyloid (Aβ) and low density lipoprotein receptor-related protein-1 (LRP1) in APP/PS1 mice after electroacupuncture (EA) treatment and further to explore the mechanism.Methods. Forty 6-month-old APP/PS1 mice were randomly divided into a model group and an EA group, with twenty wild-type mice used as a normal control group. Mice in the EA group were treated with EA at GV 20 (băi huì) and bilateral KI 1 (yŏng quán) acupoints for 6 weeks. The Morris water maze was applied to assess the spatial memory in behavior. Immunohistochemistry (IHC), ELISA, Western blotting, and so forth were used to observe the expression of LRP1 and Aβ.Results. The Morris water maze test showed that, compared with the normal control group, the model group’s learning and memory capabilities were significantly decreased (P<0.05;P<0.01). The EA group was reversed (P<0.05;P<0.01). The hippocampal expression of Aβin the EA group was significantly decreased compared to the model group (P<0.01). The expression of LRP1 in the model group was significantly lower than that in the normal control group (P<0.01); the expression in the EA group was significantly higher than that in the model group (P<0.01).Conclusions. EA therapy can improve the learning and memory capabilities of APP/PS1 mice. The underlying mechanism may lie in the upregulation of an Aβtransport receptor and LRP1.

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

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.

scholarly journals Maternal Neu5Ac Supplementation During Pregnancy Improves Offspring Learning and Memory Ability in Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
DongSheng Bian ◽  
Xinyue Wang ◽  
Jiale Huang ◽  
Xiaoxuan Chen ◽  
Hongwei Li
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Performance ◽  
Morris Water Maze ◽  
Untreated Control ◽  
Water Maze ◽  
Free Form ◽  
Morris Water Maze Test ◽  
Shuttle Box ◽  
Rat Pups ◽  
Maze Test

Sialic acids are postulated to improve cognitive abilities. This study aimed to evaluate the effects of sialic acid on behavior when administered in a free form as N-acetylneuraminic acid (Neu5Ac) to pregnant mothers or rat pups. The experiment involved 40 male 21-day-old rat pups and 20 15-day-pregnant rats that were randomized into four Neu5Ac treated groups: 0 (control), or 10, 20, and 40 mg/kg. Morris water maze test and shuttle box test were performed on the rat pups and maternal Neu5Ac-supplemented offspring on day 100 to evaluate their cognitive performance. The Neu5Ac levels in the cerebral cortex and hippocampus were tested with high-performance liquid chromatography-fluorescence detection (HPLC-FLD). We found that the maternal Neu5Ac-supplemented offspring showed better cognitive performance, less escape latency in the Morris water maze test, and less electric shock time shuttle box test, compared with the untreated control. In the meantime, the Neu5Ac level in the cerebral cortex and hippocampus of the offspring was higher in the Neu5Ac treatment group than that in the untreated control group. However, no significant differences were observed between rat pups in the treated and the untreated control groups in terms of cognitive performance and Neu5Ac content in the cerebral cortex and hippocampus. Maternal Neu5Ac supplementation during pregnancy could effectively promote the brain Neu5Ac content of the offspring and enhance their cognitive performance, but Neu5Ac had no such effect on rat pups while directly supplemented with Neu5Ac.

Abstract TP446: Rosuvastatin Improves Cerebral Hemodynamics in Rats With Chronic Cerebral Hypoperfusion

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Xiaomei Xie ◽  
Kangping Song ◽  
Li'an Huang
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Morris Water Maze ◽  
Water Maze ◽  
Caspase 3 ◽  
Treated Group ◽  
Cerebral Hypoperfusion ◽  
Morris Water Maze Test ◽  
Vehicle Group ◽  
Maze Test

Objective: Chronic cerebral hypoperfusion (CCH) is a common consequence of various cerebral vascular disorders, hemodynamics and blood composition changes, which can lead to neurodegenerative injury and cognitive dysfunction. Therefore, it is important to take measures to prevent or reverse its development. Methods: Eighty Sprague-Dawley rats were randomly divided into five groups: Sham group, Vehicle groups (2-week group and 4-week group), Rosuvastatin-treated groups (2-week group and 4-week group). Both vehicle and treated group rats were treated with bilateral common carotid artery occlusion (BCCAO). Then rats in the treated group were intravenously injection with rosuvastatin (0.2 mg/kg/day) daily for 14 days beginning 24 hours after BCCAO. The vehicle groups were given the same amount of saline. The MRI ASL technique was used to scan cerebral blood flow (CBF) at pre-occlusion, BCCAO, 1, 2, 3, and 4 weeks after operation. Morris water maze test detected spatial memory abilities of the treated and vehicle rats after BCCAO. Immunofluorescence staining was used to detect the expression of CD34, GFAP, NeuN and Caspase-3 positive cells in hippocampus. Results: CBF decreased significantly after BCCAO in both rosuvastatin-treated and vehicle groups and then increased gradually. The CBF of the treated group was basically recovered to baseline levels at 1 or 2 weeks after BCCAO. But it took the vehicle group 4 weeks to restore to baseline. The vertebral artery (VA) diameter of the treated group was greater than that of the vehicle group (p<0.05), and the recovery of CBF and the dilation of VA were more evident during the administration period. Similarly, the escape latency of the treated group rats was also less than the vehicle group in Morris Water Maze test. In addition, the number of CD34 + and NeuN + cells in the hippocampus of the treated group was more than that in the vehicle group (p<0.01), while the number of GFAP + and Caspase-3 + cells was less than in the vehicle group (p<0.01). Conclusion: Rosuvastatin can accelerate the recovery of cerebral blood flow in CCH rats, which may be related to the dilation of VAs and angiogenesis; and its effects on reducing astrocyte activation and neuroprotection may help to ameliorate cognitive dysfunction in CCH rats.

scholarly journals Effects of oral ingestion of hyoscyamine from Daturastramonium seeds on the hippocampus in adult Wistar rats (Rattusnorvegicus)

2021 ◽  
Vol 13 (2) ◽  
pp. 36-46
Author(s):  
A. T. Idris ◽  
A.M. Sunday ◽  
A.I. Ibrahim ◽  
O.N. James ◽  
A.K. Musa ◽  
...  
Keyword(s):  
Object Recognition ◽  
Morris Water Maze ◽  
Repeated Measures ◽  
Water Maze ◽  
Wistar Rats ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Novel Object Recognition ◽  
Oral Ingestion ◽  
Novel Object

The study aimed to evaluate the effects of oral ingestion of hyoscyamine fraction of Daturastramonium seeds on the hippocampus in adult Wistar rats. Fresh seeds of D. stramonium were procured and fractionated using high-performance liquid chromatography (HPLC). Twenty-four healthy adult Wistar rats weighed 230±0.50 grams, were procured and divided equally into four groups for the experiment. The group one received an equivalent bodyweight of normal saline, while three other groups received 200, 400 and 800 mg/kgbwt of hyoscyamine fraction of D. stramonium respectively for three weeks. At the end of the experiment, the animals were subjected to memory test using Morris water maze (MWM) and Novel object recognition test (NORT) test paradigms. The data obtained were expressed as mean ± SEM and repeated measures ANOVA with Fisher’s multiple comparisons post-hoc tests were used to obtain mean differences using Minitab 17 (LLC., U.K.) statistical package software. P < 0.05  was considered statistically significant. There was a statistically significant increase in the exploration time (p = 0.031) and escape latency period (p < 0.001) in the novel object recognition and Morris water maze test between the groups in the treated compared to the control group. The CA3 region of the treated group showed significant neuronal lesions, cytoplasmic vacuolations, pyknosis and necrosis. . In conclusion, exposure to hyoscyamine fraction of D.stramonium at adulthood impaired memory in Wistar rats.  

scholarly journals Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Rat Model ◽  
Gut Microbiome ◽  
Water Maze ◽  
Single Injection ◽  
Postoperative Cognitive Dysfunction ◽  
Aged Rats ◽  
Short Term ◽  
Term Memory

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

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

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.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
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.

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

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.

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