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

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Akinori Higaki ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Li-Juan Min ◽  
Harumi Kan-no ◽  
...  

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.

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0191708 ◽  
Author(s):  
Akinori Higaki ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Li-Juan Min ◽  
Hui-Yu Bai ◽  
...  

2021 ◽  
Vol 5 (1) ◽  
pp. 009-015
Author(s):  
CC Mfem ◽  
SA Seriki

Background/aim: Amitriptyline belongs to class of known as tricycline antidepresant (TCA) that is being used to treat anxiety and depressive states. It may help improve mood and feelings of well-being, relieve anxiety and tension, help to improve sleep and increase energy level. The study investigated the effect of amitriptyline on learning and memory using eighteen (18) healthy Swiss mice of both sexes weighing 16 – 25 g. Method: The animals were divided into three (3) groups consisting of six (6) animals each. Group 1 served as the control group, Group 2 was administered with amitriptyline at a dose of 3 mg/kg body weight dissolved in 3 mls of distilled water, and used to test for learning, while Group three was also given similar administration like Group 2, but used to test for memory. All the animals were tested for learning and memory performance using Novel object recognition task and Morris water maze test. Results: The results obtained from the Novel object recognition task showed that there was a significant decrease (p < 0.05) in total object approach in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant decrease (p < 0.05) in retention trial of amitriptyline group when compared to retention trial in the control group. There was a significant decrease (p < 0.05) in total duration exploring objects in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant increase (p < 0.05) in total duration exploring objects in retention trial of amitriptyline treated group when compared to the retention trial of the control group. There was a significant decrease (p < 0.05) in the index of habituation of amitriptyline treated group when compared to the control group. The index of discrimination showed a significant increase (p < 0.05) in amitriptyline treated group when compared to the control group and a significant decrease (p < 0.05) in amitriptyline group when compared to the control group. In the Morris water maze test, Day 1 – 3 were for acquisition training, day 4 – 6 reversal training, day 7 the probe trial day and day 8 the visible platform day. During acquisition training in the Morris water maze test, there was no significant difference in Swim latencies in day 1 and 2. However in day 3, there was a significant increase (p < 0.05) in swim latency of group compared to control group and a significant decrease (p < 0.05) in swim latency of amitriptyline treated group compared to the control group. During reversal training in day 1, 2 and 3, there was no significant difference in swim latency among the three groups. Results for the retention quadrant in the probe trials showed a significant decrease (p < 0.01) in amitriptyline group when compared to the control group. Conclusion: Results suggest that amitriptyline impairs learning and memory functions.


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.


2015 ◽  
Vol 22 (4) ◽  
pp. 34-38
Author(s):  
Косолапов ◽  
V. Kosolapov ◽  
Трегубова ◽  
I. Tregubova ◽  
Спасов ◽  
...  

The data of studies of the new antioxidant agent Enoxifol (2‐(3,4‐dioxyphenyl)‐9‐ diethylaminoethylimidazo[1.2‐a] benzimidazole dihydrobromide) (10 mg/kg) action on spatial orientation and memory in rats using Morris test in comparison to Mexidol (2‐ethyl‐6‐methyl‐3‐oxypyridine succinate) (100 mg/kg) are presented. Morris water maze test is widely used to evaluate spatial orientation and memory in experimental animals. Mexidol was taken as the native etalon antioxidant drug having the wide spectrum of psychotropic activities. It was shown that Enoxifol significantly 3 fold diminished the time of platform finding at the first day of investigation. Mexidol has a tendency to decrease that index as well. At the second day of testing only Mexidol allowed rats to keep the memorable track, and the time of platform finding was similar to those in the fourth try at the fist day. Enoxifol significantly 4.88 fold increased the rate of reproduction of the information in the repeated study from the first to the fourth try. Thus the conducted experiments allowed to establish the effective action of Mexidol and Enoxifol at the different stages of the memorable track formation and ability of animals for leaning.


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