Role of the p38MAPK signaling pathway in hippocampal neuron autophagy in rats with chronic intermittent hypoxia

2021 ◽  
Author(s):  
Yuxin He ◽  
Zhili Liu ◽  
Yinpei Huang ◽  
Bing Li
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Water Maze ◽  
Intermittent Hypoxia ◽  
Hippocampal Neuron ◽  
Morris Water Maze Test ◽  
Chronic Intermittent Hypoxia ◽  
Maze Test ◽  
P38mapk Signaling

This study explored the role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in hippocampal neuron autophagy in rats with chronic intermittent hypoxia (CIH). Sixty-four male Sprague-Dawley rats were randomly divided to normoxic control (CON), CIH (subdivided into groups A, B, and C undergoing intermittent hypoxia for 2, 4, and 6 weeks, respectively), solvent (CIH+Veh), or p38MAPK inhibitor (CIH+SB203580) groups. DMSO and SB203580 were injected intraperitoneally 30 min before hypoxia in CIH+Veh and CIH+SB203580 group rats, respectively. Rat learning and memory were evaluated via the Morris water maze test. Ultrastructural changes in the hippocampal CA1 region autophagic vesicles and neurons were observed under transmission electron and light microscopy. Hippocampal microtubule-associated proteins were detected by western blot. Morris water maze test showed that CIH+SB203580 group rats spent significantly more time on the platform quadrant and crossed the platform more times than CIH+Veh group rats (P < 0.01). HE staining showed greater rat cell damage in the CIH+SB group than in the CIH and CIH+Veh groups. Western blot analysis showed that CIH+SB group rats had significantly lower p-p38MAPK/p38MAPK, LC3I, and p62 expression and higher beclin-1 expression than CIH+Veh group rats (P < 0.01). Electron microscopy showed that CIH+SB203580 group rats had several small hippocampal neuron autophagic vesicles. On immunofluorescence analyses, it showed a higher LC3II expression in CIH+SB203580 group rats than in CIH+Veh group rats (P < 0.01). These results indicate that inhibition of the CIH p38MAPK signaling pathway can activate autophagy and protect hippocampal neurons in rats.

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.

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.

Beta-caryophyllene, a CB2R selective agonist, protects against cognitive impairment caused by neuro-inflammation and not in dementia due to ageing induced by mitochondrial dysfunction

2021 ◽  
Vol 20 ◽  
Author(s):  
Urja Kanojia ◽  
Shrikant Gyaneshwar Chaturbhuj ◽  
Runali Sankhe ◽  
Maushami Das ◽  
Raviteja Surubhotla ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Water Maze ◽  
Recognition Task ◽  
Morris Water Maze Test ◽  
Novel Object Recognition ◽  
Object Recognition Task ◽  
Sd Rats ◽  
Maze Test ◽  
Novel Object Recognition Task ◽  
Neuro Inflammation

Background: Dementia is a neurodegenerative disorder majorly evidenced by cognitive impairment. Although there are many types of dementia, the common underlying etiological factors in all the types are neuro-inflammation or ageing induced apoptosis. β-caryophyllene, a cannabinoid type-2 receptor agonist has reported to have promising neuroprotective effects in cerebral ischemia and neuro-inflammation. Objective: In the present study, we evaluated the effects of β-caryophyllene, against animal models of dementia whose etiology mimicked neuro-inflammation and ageing. Method: Two doses (50 and 100 mg/kg of body weight) of β-caryophyllene given orally were tested against AlCl3-induced dementia in male Sprague Dawley (SD) rats using Morris water maze test. Subsequently, the effect of the drug was assessed for episodic memory in female SD rats using novel object recognition task in doxorubicin-induced neuro-inflammation and male SD rats for chemobrain model. Moreover, its effects were evaluated in D-galactose-induced mitochondrial dysfunction leading to dementia. Results: β-caryophyllene, at both the doses, showed significant improvement in memory when assessed using parameters like target quadrant entries, escape latency and path efficiency in Morris water maze test for spatial memory. In the doxorubicin-induced chemobrain model, β-caryophyllene at 100 mg/kg significantly elevated acetylcholinesterase and catalase levels and lowered lipid peroxidation compared to the disease control. In the novel object recognition task, β-caryophyllene at 100 mg/kg significantly improved recognition index and discrimination index in the treated animals compared to the disease control, with a significant increase in catalase and decrease in lipid peroxidation in both hippocampus and frontal cortex. However, in D-galactose-induced mitochondrial dysfunction model, β-caryophyllene failed to show positive effects when spatial memory was assessed. It also failed to improve D-galactose induced diminished mitochondrial complex I and II activities. Conclusion: Hence, we conclude that β-caryophyllene at 100 mg/kg protects against dementia induced by neuro-inflammation with no effect on neuronal aging induced by mitochondrial dysfunction.

Sign in / Sign up

Export Citation Format

Share Document