scholarly journals Effect of Metformin on Some Cognitive Functions in Old Rats

Author(s):  
Mohammad Pak-Hashemi ◽  
Mahsa Hassanipour ◽  
Ayat Kaeidi ◽  
Pooya Saeed-Askari ◽  
Iman Fatemi ◽  
...  

Introduction: Aging is a complex process and is considered as a risk factor for many diseases such as hypertension, Alzheimer, cancer, depression and anxiety. Recently, it has been shown that metformin, an anti-diabetic drug, has important neurological effects such as preventing memory loss, stroke, anxiety, inflammation and seizures. Therefore, the aim of this study was investigating the effects of metformin on some cognitive factors in elderly male rats. Methods: 24 rats (22 months) were randomly divided into 3 groups (n=8). The first group was the control group that received water orally, the second group received metformin 1 mg/kg orally and the third group received metformin 10 mg/kg orally. After treatment for 40 days (once daily), behavioral tests, including Y-maze, elevated plus maze and depression test were performed on animals. Results were analyzed using GraphPad Prism version 6 and One-way ANOVA followed by Tukey-post hoc test. Results: The results of this study showed that metformin at a dose of 10 mg/kg significantly reduced anxiety (P<0.001) and depression (P<0.001) in older animals. Metformin at a dose of 1 mg/kg failed to improve aging-related disorders in this model. Conclusion: Metformin at a dose of 10 mg/kg can reduce the quality of life by reducing anxiety and depression.

2020 ◽  
pp. 109-114

Background and Objectives: Kaempferol (KM) is one of the most important plants with neuroprotection and analgesic effects. In addition, bicuculline (BIC) is a competitive antagonist of the GABAA ionotropic receptor (the most important targets of benzodiazepines and other anxiety suppressants). In this study, intracerebroventricular microinjection of KM on anxiety and its interaction with GABAergic mechanism were investigated in male rats. Materials and Methods: In this exploratory investigation, the male rats were divided into the following groups: control (saline), groups treated by KM (0.5 and 2 mg/rat), DMSO (1mg/rat), KM 0.5+BIC1 mg/rat, KM 0.5+BIC4 mg/rat, KM 2+BIC1 mg/rat, BIC groups (1, 4 mg/rat), and KM 2+BIC 4 mg/rat. Besides, an elevated plus-maze paradigm was used for the evaluation of the anxiety. Results: Statistical analysis revealed that the indices of TTOA in KM groups (0.5 and 2 mg/rat) significantly increased in comparison to the control group (P<0.05 and P<0.01, respectively). Moreover, regarding the involvement of the GABAergic system in the anxiolytic-like activity of KM, it was demonstrated that the TTOA related to co-administration of KM (0.5mg/rat) with bicuculline (1mg/rat) significantly reduced, compared to the control group (P<0.05). Conclusion: According to the obtained results, the use of KM can likely improve anxiety through GABAergic mechanism(s).


2020 ◽  
Vol 10 (3) ◽  
pp. 152
Author(s):  
Ibrahim Alharbi ◽  
Hindi Alharbi ◽  
Yasser Almogbel ◽  
Abdullah Alalwan ◽  
Ahmad Alhowail

Doxorubicin (DOX) is widely used to treat many types of cancer; however, it is associated with chemotherapy-related complications such as cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are currently no available therapeutic options. This study aims to examine whether metformin (MET) can protect against the neurotoxicity caused by DOX treatment. Forty male rats were divided into four groups (10 rats/group): control, DOX, DOX + MET, and MET. Rats treated with DOX received five doses of 4 mg/kg DOX weekly (cumulative dose: 20 mg/kg). For the DOX-MET and MET groups, MET (3 mg/mL) was dissolved in drinking water. Behavioral and glucose tests were performed one day after treatment was completed. We found DOX (4 mg/kg/week, 5 weeks) caused learning and memory impairment in the Y-maze, novel object recognition, and elevated plus maze behavioral tests. MET did not rescue these DOX-induced memory impairments. Neither DOX nor MET nor MET + DOX altered glucose levels following the treatment. In summary, DOX treatment is associated with memory impairment in rats, but MET does not rescue this cognitive dysfunction.


2005 ◽  
Vol 93 (5) ◽  
pp. 613-618 ◽  
Author(s):  
Takahiro Kawasaki ◽  
Akiko Kashiwabara ◽  
Tadashi Sakai ◽  
Kanji Igarashi ◽  
Nobuyuki Ogata ◽  
...  

The current epidemic of diabetes likely reflects marked changes in environmental factors, although genetic susceptibility plays a powerful role in the occurrence of diabetes in certain populations. We investigated whether long-term sucrose-drinking causes hyperglycaemia in male Wistar-Imamichi littermates (n 32), which are not genetically susceptible to diabetes or obesity. Each litter was divided equivalently into two groups, the sucrose group and the control group. The sucrose group received 300 g/l sucrose water and the control group received regular water until 42 weeks of age. Rats were weighed every 1 or 2 weeks. Oral glucose tolerance tests were performed at 28 and 36 weeks of age. Plasma glucose and insulin concentrations were measured. Body weights were significantly greater in the sucrose group than in the control group in 18-week-old rats (P<0·05), and the difference between the two groups reached 163 g by the end of the study (P<0·01). The 120 min post-load plasma glucose concentration in the sucrose group was 11·4 (sd 2·8) mmol/l in 28-week-old rats and 12·7 (sd 2·2) mmol/l in 36-week-old rats, while that of the control group remained approximately 7·3–7·7 mmol/l. In the sucrose group, the plasma insulin peak occurred 30 min post-load at 28 weeks of age; but the peak disappeared and hyperinsulinaemia was prolonged at 36 weeks of age. In conclusion, long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats.


2021 ◽  
Author(s):  
Hesam Parsa ◽  
Tayebeh Shiravand ◽  
Kamal Ranjbar ◽  
Alireza Komaki

Abstract Background: Diabetes mellitus is one of the most important causes of Alzheimer’s disease and dementia. Portulaca oleracea (P.oleracea) is a rich source of antioxidants, which reduces inflammation and oxidative stress in diabetic rats. Exercise training has also been shown to improve mental function and enhance learning and memory efficacy. Therefore, this study was designed to explore the potential combined effect of P. oleracea and exercise training on neurobehavioral dysfunction in streptozotocin (STZ)-induced diabetic male rats. Methods: For this purpose, 50 male Wistar rats were divided into five groups: 1) healthy control group (Con), 2) sedentary diabetic group (D), 3) diabetic rats treated with P. oleracea(D+Po), 4) diabetic rats treated with exercise training (D+Ex), and 5) diabetic rats treated with P.oleracea and exercise training (D+Po+Ex) simultaneously. Animals in the exercise groups were subjected to progressive swimming training for 12weeks. P.oleracea was mixed with standard pellet food for 12weeks. Neurobehavioral dysfunction was investigated by elevated plus-maze, shuttle box, open field, and novel object recognition tests.Results: Compared with the normal control group, rats in the sedentary diabetic group showed a more passive avoidance memory deficit and more anxiety, and less exploration. Due to exercise training and treatment with P. oleracea, the neurobehavioral deficit in the trained diabetic rats receiving P. oleracea reached the normal levels of those in the healthy group.Conclusion: These data demonstrated that diabetes causes significant neurobehavioral deficit. Nevertheless, swimming training and P. oleracea synergistically ameliorate and reverse the neurobehavioral deficit in STZ-induced diabetic male rats.


Background: This study aimed to compare the two methods of continuous and interval training for eight weeks on Aplin 13 and fibroblast growth factor in elderly rats. Materials and Methods: In this study, 30 elderly male rats were randomly divided into three groups of continuous training (n=10), interval training (n=10), and control group (n=10). Interventions were performed for eight weeks. Blood samples (3 cc) were taken from the tails of elderly male rats 72 h before and after the last session of the protocol to evaluate the research variables (Aplin 13 and fibroblast growth factor). One-way analysis of variance was used to analyze the findings, and the Tukey test was utilized for the homogeneity of variance of groups. All statistical tests were performed in SPSS software (version 17) at a significance level of α=0.05. Results: Aplin 13 had a significant increase in the continuous exercise group (P<0.05). Moreover, the fibroblast growth factor was significantly increased in the continuous exercise group (P<0.05). Aplin 13 had a significant increase in the interval exercise group (P<0.05). Fibroblast growth factor was significantly increased in the interval exercise group (P<0.05). No significant changes were observed in the control group. Conclusion: The results of this study showed that eight weeks of continuous and interval training caused a significant increase in the levels of Aplin 13 and fibroblast growth factor in elderly male rats. Therefore, these exercises and especially periodic exercises can be used as a suitable way to increase angiogenesis in the elderly.


Author(s):  
CHANCHAL THAKUR ◽  
VRISH DHWAJ ASHWLAYAN

Objective: The objective of the study was to assess the neuroprotective effect of azilsartan as a memory enhancer against scopolamine-induced amnesia in rats. Methods: Albino Swiss male rats in equal numbers per group (n=6) were taken. Scopolamine hydrobromide was administered to induce amnesia within the rats. Control group rats were administered normal, negative control groups were administered with scopolamine to induce amnesia and nitrite during trials, positive control group rats were administered piracetam+ scopolamine and piracetam nitrite during trials, and test control group rats were administered azilsartan +sodium nitrite and azilsartan nitrite. Exteroceptive behavioral models just like the elevated plus-maze model, Morris water maze model, acquisition trials, and retrieval trial were wont to evaluate the neuroprotective effect of azilsartan. Results: The scopolamine and azilsartan have a significantly decreasing effect on time spent within the target quadrant (TSTQ) but piracetam has an increasing effect. The effect of azilsartan on transfer latency time (TLT) was observed against scopolamine-induced amnesia in rats using the elevated plus-maze test. Piracetam was found to decrease the TLT and restore memory function at a better dose. Within the case of scopolamine treated rats, a big increase in TLT was noted. Azilsartan treated group also increased TLT within the elevated plus maze. It is noted that the scopolamine features a significantly increasing effect on escape latency time (ELT). Piracetam features a decreasing effect on ELT. A rise in ELT was seen because of azilsartan. Conclusion: This study suggested that the azilsartan features a significant decreasing effect on TSTQ, azilsartan treated group also increased TLT and ELT.


Author(s):  
Yu. V. Halahan ◽  
O. Ye. Маievskyi ◽  
Yu. Y. Guminskyi ◽  
A. P. Korol ◽  
S. V. Prokopenko

Disruption of the metabolism of the essential amino acid methionine causes the syndrome of hyperhomocysteinemia. This pathological condition is associated with the risk of developing a number of diseases, including chronic liver disease. The mechanisms of liver tissue damage in hyperhomocysteinemia remain poorly understood and require more detailed study. The aim of the study is to establish the features of submicroscopic changes in the liver structure of old rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear old (24-26 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the lungs of rats was performed using an electron microscope PEM-125K. At experimental hyperhomocysteinemia in a liver of old rats there are changes in all structural components. Mitochondrial destruction and edema were observed in the vascular endothelium. Organelles have an enlightened matrix, a reduced number of cristae. A significant content of destructively altered mitochondria in endothelial cells indicates a failure of adaptation mechanisms. Erythrocyte sludges are observed in the lumens of the sinusoids. The number of fat-accumulating cells decreases, which indicates their transformation into fibroblasts and leads to the growth of collagen fibers, expansion of the sinusoidal spaces and the development of stromal fibrosis.


2017 ◽  
Vol 87 (1-2) ◽  
pp. 59-65 ◽  
Author(s):  
Saeed Samarghandian ◽  
Mohsen Azimi-Nezhad ◽  
Tahereh Farkhondeh

Abstract. The present study was designed to investigate the changes in activities of antioxidant enzymes and lipid peroxidation level in the liver of 2, 10 and 20 months old rats, and to see whether these changes are restored to those of the two month old rats after carvacrol treatment. Male rats of 2, 10, and 20 months (n = 10 for each group) were used for all the experiments. The aged rats (10 and 20 months old) were given carvacrol (15 mg/day per body weight) for 30 days. Control animals received an equal volume of vehicle. After the treatment, livers were removed for estimation of superoxide dismutase-SOD, glutathione-S-transferase-GST, catalase-CAT activities and lipid peroxidation level. The present findings determined that normal aging was associated with a significant decrease in the activities of antioxidant enzymes (SOD; 11.87 ± 0.6 (2 months old) vs 7.56 ± 0.1 (20 months old); P < 0.001) in liver, as well as an increase in lipid peroxidation level (MDA; 0.15 ± 0.01 (2 months old) vs 0.41 ± 0.01 (20 months old); P < 0.001) in aged rats. Also, the results of this study indicated that carvacrol treatment increased the activities of the antioxidant enzymes in 20 months old animals versus the aged matched control group (SOD; 9.87 ± 0.4; P < 0.01). Furthermore, carvacrol decreased lipid peroxidation content in 10 and 20 months old animals compared with the aged matched control (MDA; 9.87 ± 0.4; P < 0.001). Our data shows that carvacrol could be a candidate to inhibit the development of age-induced liver damage through inhibition of oxidative stress and also increasing antioxidant defenses.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Fatma Sobhy Ibrahim ◽  
Lobna Fouad Abdel-Aziz ◽  
Wesam Mostafa Elbakly ◽  
Nesreen Hamdy El Gayar

Abstract Alzheimer disease (AD) is a chronic and progressive neurodegenerative disorder characterized by memory loss and cognition impairment. A link has been established between AD and epilepsy sharing multiple mechanisms and pathogenesis. Similar Hippocampal changes have been found between both diseases. Choosing antiepileptic drug in AD patient represent a great a challenge especially with increase seizure risk in AD patients. Lacosamide, antiepileptic drug, was reported to have a neuroprotective effect in animal models and a histone deacetylase inhibition activity. This study was designed to investigate the potential effect of chronic lacosamide treatment in Streptozotocin induced AD in male Wistar rats. Methods AD animal model was induced with single bilateral intracerebroventricular injection of STZ (3 mg/kg) on day one. Lacosamide (30 mg/kg orally, once daily) was administrated for 21 days. Cognitive function assessment was done with Morris Water Maze (MWM) and Y Maze tasks. APP and MAPT mRNA level were measured. Results ICV-STZ caused significant prolongation in Escape latency time and reduction in time spent in target quadrant in MWM and reduction in spontaneous alteration ratio in Y Maze compared to control group. STZ induced Up-regulation in Amyloid precursor protein and Microtubule associated protein tau gene expression. Chronic Lacosamide treatment attenuated STZ induced cognitive impairment and mitigated APP and MAPT induced expression with STZ. Conclusion Lacosamide has a neuroprotective effect against STZ induced cognitive deficits ameliorating Aβ and Tau pathology.


Author(s):  
Rima Benatoui ◽  
Abdelmadjid Bairi ◽  
Abdelkrim Tahraoui

Objective: During the last decade, the role of the β-carboline alkaloid harmine has essentially been studied with regard to its anxiolytic effect, as it was done in our laboratory; therefore, this study has been progressed to cover the effect of this alkaloid on pregnant wistar rats.Methods: The molecule was used at doses of 10 mg/kg, 15 mg/kg, pregnant female rats were divided into three groups according to the stage of pregnancy: first, second, and the third week of pregnancy. Each group has been subdivided into seven subgroups: control group, two treated groups with harmine, acute footshock stress at 1,2mA, sub-acute footshock stress at 0,4mA, psychological stress, and the treated group that footshocked after with 1,2mA, all groups were carried out open field test, plus maze test and light/dark box test.Results: Thigmotaxis is reflected by the significant increase in the traveled distance in peripheral area in the open field of the three groups ‘weeks’ at dose of 10 mg/kg, the enhancement in the number and time of rearing, at both doses, during the second and the last week, the significant increase in the number of entries ‘in open arms’ in plus-maze during the first and third weeks at 15 mg/kg, and the significant decreased in time spent in the light compartment of the light/dark box at the same dose of all groups ‘weeks’ were noticed, which confirm the anxiolytic effect of the alkaloid, even in the case of the footschock stressed pregnant rats of all groups ‘weeks’ that enhancement of number of enties into open arms during the plus maze test.Conclusion: So we can conclude that the anxiolytic effect of harmine not shortening to male rats, but expands to female pregnant wistar rats, and establishes its effect by diminishing time in light compartment of light/dark box and number of entries in open arms of plus maze, in other hand, the increase in the number and the time of rearing reflects the enhancement of exploratory behavior.


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