scholarly journals Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats

2018 ◽  
Vol 76 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Yousef Baghcheghi ◽  
Mahmoud Hosseini ◽  
Farimah Beheshti ◽  
Hossein Salmani ◽  
Akbar Anaeigoudari

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

2011 ◽  
Vol 39 (03) ◽  
pp. 551-563 ◽  
Author(s):  
Chuan-Sung Chiu ◽  
Yung-Jia Chiu ◽  
Lung-Yuan Wu ◽  
Tsung-Chun Lu ◽  
Tai-Hung Huang ◽  
...  

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated. Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice. These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14679-e14679
Author(s):  
Shengjun Ji ◽  
Ming Yang ◽  
Jinming Yu

e14679 Background: This study aimed to investigate the role of neurotrophin receptor TrkA in cranial radiation-induced memory decline. Methods: Single dose of 10Gy 4MeV electron beam whole brain irradiation (WBI) was given to young male Sprague-Dawley rats (50–60g, day 21). 3 months after WBI, western blot was performed to detect protein level of TrkA and its downstream signaling molecules. The Morris water maze test was performed to evaluate the consequence of WBI on hippocampus-dependent memory formation. Immunohistochemistry was performed to evaluate the consequence of WBI on neurogenesis. For overexpression of TrkA, Adeno-associated virus were injected at the rate of 0.2μl/min (n = 15-20 per group). After that, Morris water maze test was performed again. Results: In Morris water maze test, WBI lead to notable memory deficit, the irradiation rats spent longer latency time than control rats (p < 0.05). In the spatial probe trial, the irradiation rats spent less time in the target quadrant than control rats (p < 0.05). Immunohistochemistry showed that cranial irradiation inhibited proliferation and neurogenesis in hippocampus. The protein level of TrkA expression decreased significantly at 3 months after irradiation compared with control group. Phosphorylation of PI3k, AKT, ERK1/2, CREB were also observed to be significantly inhibited (all p < 0.05). Next, we explored the irradiation-induced apoptotic signal transduction. The increased expression of JNK, caspase-3/9 and reduced expression of BCl2 confirm the irradiation induced apoptosis. After Adeno-associated virus injection, AAV-overexpression TrkA rats showed less escape latency time (p < 0.05) and spent more time (p < 0.05) in the target quadrant than AAV-irradiation rats, but still more escape latency time (p < 0.05) and spent less time (p < 0.05) in the target quadrant than AAV-control rats. Additionally, immunofluorescence staining showed AAV-overexpression-TrkA also rescued radiation-induced neurogenesis impairment Conclusions: TrkA may play a critical role in radiation-induced memory deficit, which indicate the data may have important therapeutic implications.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jiling Huang ◽  
Zhigang Gong ◽  
Yingnan Kong ◽  
Yanwen Huang ◽  
Hui Wang ◽  
...  

Objective. To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. Methods. Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4) and treatment groups including EA group (CCl4 + EA), lactulose group (CCl4 + Lac), and EA plus lactulose group (CCl4 + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl4 + Lac and CCl4 + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl4 groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl4 + EA and CCl4 + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. Results. Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-α, IL-1β, IL-6, iNOS, TLR4, MyD88, NF-κB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-α, IL-6, TLR4, MyD88, NF-κB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. Conclusion. EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-κB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Jiang ◽  
Gang Liu ◽  
Suhua Shi ◽  
Zhigang Li

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.


2021 ◽  
Vol 19 ◽  
Author(s):  
Tingting Pi ◽  
Guangping Lang ◽  
Bo Liu ◽  
Jingshan Shi

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.


2013 ◽  
Vol 411-414 ◽  
pp. 3178-3180
Author(s):  
Li Hai Jin ◽  
Xing Yu Zhao ◽  
Wei Zhang ◽  
Wei Chen ◽  
Guo Qing Sun ◽  
...  

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.


Author(s):  
Urja Kanojia ◽  
Shrikant Gyaneshwar Chaturbhuj ◽  
Runali Sankhe ◽  
Maushami Das ◽  
Raviteja Surubhotla ◽  
...  

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.


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