Chronic immobilization stress induces anxiety-related behaviors and affects brain essential minerals in male rats

Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Gulsah Bitgul ◽  
Isil Tekmen ◽  
Didem Keles ◽  
Gulgun Oktay

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n=7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
M. Raeeszadeh ◽  
P. Mortazavi ◽  
R. Atashin-Sadafi

Nicotine is one of the most important compounds in cigarette which can cause changes in the concentration of neurotransmitters and damage to the nervous system. The aim of this study was to investigate the effect of the hydroalcoholic extract of Medicago Sativa L. (alfalfa) on controlling nicotine-induced brain damage and anxiety behaviour in rats. Forty-two male Wistar rats were randomly divided into six equal groups and treated daily as follows: a control group, T1 and T2 groups where animals were subcutaneously injected 250 and 500 mg/kg alfalfa extract, respectively, T3 and T4 groups where animals were injected subcutaneously 0.2 mg/kg nicotine and 250 and 500 mg/kg alfalfa extract, and T5 group in which only nicotine at the dose of 0.2 mg/kg was injected. At the end of the period after weighing, the elevated plus-maze test was taken from the animals. Serum assay was conducted to measure TCA, IL-1, and TNFα, and half of the brain tissue was used to measure oxidative stress parameters (GPx, SOD, TAC, and MDA) and the other parts were used for histopathological studies. Body weight in the T5 group was significantly different from that of the other groups. The time and number of open arms reduced in the T5 group. The duration and number of times in the open arm significantly decreased in the treated groups in a dose-depended manner. Malondialdehyde concentration was the highest in the nicotine group and the lowest in T2. The concentration of GPx and SOD was significantly increased in the presence of alfalfa extract in nicotine groups. TNFα and IL-1 in the T5 group showed a significant increase compared to the other groups. Moreover, the number of neurons and the level of necrotic neurons and gliosis significantly decreased and increased in the nicotine group, respectively, while these histopathological damages improved by treatment with alfalfa extract in T3 and T4 groups. Alfalfa extract can have a significant dose-dependent therapeutic effect on inducing oxidative damage and inflammatory responses of nicotine in the brain and reducing anxiety behaviours.


Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Funda Gulcu Bulmus ◽  
Ozgur Bulmus ◽  
...  

Abstract Objectives Reproduction is one of the physiological functions that are often negatively affected by chronic stress. We aimed to examine effects of two distinct 7-day chronic immobilization stress (IMO) models on gonadotropins levels and depression-like behaviors in female rats. Methods Adult Wistar albino female rats were divided into three groups as follows (n=7 for each group): control, IMO-1 (45 min daily for 7-day) and IMO-2 (45 min twice a day for 7-day). Neuropsychiatric behaviors were determined by using forced swimming test (FST) and open field test (OFT). Gonadotropins were analyzed using ELISA tests. Results In FST, swimming was lower, and immobility was higher in the IMO-1 group and IMO--2 group. Climbing score of the IMO-2 group was higher compared to the control group. In OFT, there was no significant alteration in the mean velocity, total distance, duration of time spent in the central area and duration of latency in the central area between the stress groups and the control group. Final body weight and percentage of body weight change were lower in both stress groups. The follicle-stimulating hormone level was lower only in the IMO-2 group, and the luteinizing hormone concentrations were significantly lower in the IMO-1 group and IMO-2 group. Conclusions Our results indicated that depression-like behaviors increased, and gonadotropins decreased in the female rats exposed to 7-day chronic IMO.


Drug Research ◽  
2017 ◽  
Vol 68 (01) ◽  
pp. 33-37 ◽  
Author(s):  
Hamed Ghavimi ◽  
Sara Darvishi ◽  
Saeed Ghanbarzadeh

Abstract Background Dependence and tolerance to morphine are major problems which limit its chronic clinical application. Purpose This study was aimed to investigate the attenuation effect of Cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,), on the development of Morphine-induced dependence and tolerance. Methods Male Wistar rats were selected randomly and divided into different groups (n=8) including: a control group, groups received additive doses of morphine (5–25 mg/kg, ip, at an interval of 12 h until tolerance completion), and groups pretreated with Cerebrolysin (40, 80 and 160 mg/kg, ip, before morphine administration). Development of tolerance was assessed by tail-flick test and the attenuation effect of Cerebrolysin on morphine-induced dependence was evaluated after injection of naloxone (4 mg/kg, ip, 12 h after the morning dose of morphine). Seven distinct withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, wet dog shake and teeth grinding were recorded for 45 min and total withdrawal score (TWS) was calculated. Results Results showed that administration of Cerebrolysin could prolonged development (10 and 14 days in administration of 80 mg/kg and 160 mg/kg Cerebrolysin) and completion (4, 10 and 14 days in administration of 40, 80 and 160 mg/kg Cerebrolysin, respectively) of tolerance. Results also indicated that administration of Cerebrolysin (40, 80 and 160 mg/kg) could significantly decreased the TWS value (62±2, 77±4 and 85±6%, respectively). Conclusion In conclusion, it was found that pretreatment with Cerebrolysin could attenuated morphine-induced tolerance and dependence.


Biologia ◽  
2014 ◽  
Vol 69 (10) ◽  
Author(s):  
Hana Ďúranová ◽  
Monika Martiniaková ◽  
Ivana Boboňová ◽  
Radoslav Omelka ◽  
Robert Stawarz ◽  
...  

AbstractCadmium (Cd) and diazinon (DZN) are known to be environmental risk factors for various bone diseases including osteoporosis. Selenium (Se), an essential constituent of many antioxidant enzymes, has in higher concentrations negative effects on the bone. The present study was aimed to investigate possible changes in femoral bone of adult male rats after their acute and subchronic exposures to Cd, DZN and Se. A total of 30 male Wistar rats were randomized into three experimental groups. The rats in the group A (4-months-old) were injected intraperitoneally with a mixture of 2 mg CdCl2 kg−1, 20 mg DZN kg−1 and 2 mg Na2SeO3 kg−1 body weight and killed 36 h after xenobiotics had been injected. In the group B, young males (1-month-old) were administered with a combination of 30 mg CdCl2 L−1, 40 mg DZN L−1 and 5 mg Na2SeO3 L−1 in their drinking water, for 90 days. Ten 4-months-old males without toxicant supplementation served as a control group (C). After treatment period, detailed histological analysis of femoral bone was performed in each group. Our results revealed apparent osteoporotic symptoms (resorption lacunae, osteoporotic fractures) in rats from groups A and B. Moreover, histomorphometrical evaluation showed reduced bone vascularization (constricted primary osteons’ vascular canals and Haversian canals) and weakness mechanical properties of bones (smaller size of the secondary osteons) in these rats in comparison with those of the control group. Our study demonstrates for the first time that acute and subchronic co-administrations to Cd, DZN and Se induce evident manifestation characteristics of osteoporosis in male rats.


2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.


2021 ◽  
Vol 7 (1) ◽  
pp. 42-50
Author(s):  
Zahra Nazari Barchestani ◽  
◽  
Maryam Rafieirad ◽  

Background: Ischemia causes severe neuronal damage and induces oxidative stress, memory impairment, and reduces pain threshold. Herniarin is a powerful antioxidant. Objectives: This study aimed to evaluate the effect of herniarin on memory, pain, and oxidative stress in an ischemia model in male rats. Materials & Methods: In this study, 50 male rats were divided into 5 groups of control, sham, ischemic, and two other ischemic groups, which received herniarin at doses of 150 and 300 mg/kg by gavage for 14 days. Behavioral tests were performed by shuttle box, and Y-maze and pain tests were performed by Tail-Flick test. Then, the rats’ brains were extracted to evaluate lipid peroxidation and measure the levels of thiol and Glutathione Peroxidase (GPX) in the hippocampus and striatum tissues. The results were expressed as Mean±SEM and then analyzed using suitable statistical methods of ANOVA and least significant difference post-hoc test in SPSS V. 20. Results: Herniarin significantly increased the avoidance memory, spatial memory, and pain thresholds of ischemic rats at different concentrations (P<0.001). Besides, the amount of malondialdehyde (MDA) and thiol in the ischemic group increased significantly in comparison to the control group (P<0.001). Also, in the ischemic group, GPX (P<0.001) significantly decreased. Decreased MDA (P<0.001) and thiol (P<0.001) and increased GPX levels were observed with herniarin administration (P<0.01). Conclusion: According to this study’s results, herniarin can remove free radicals and oxidant substances from the brain. Thus, it improves memory and pain thresholds in the brain hypoperfusion ischemia model.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Yulia A. Pogorelova ◽  
Ekaterina I. Surikova ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Irina V. Kaplieva ◽  
...  

e23516 Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p<0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p<0.05), E2 and P4–by 3.5 times (p<0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p<0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p<0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p<0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.


Synapse ◽  
2019 ◽  
Vol 73 (5) ◽  
pp. e22088 ◽  
Author(s):  
Batsheva Reich ◽  
Yan Zhou ◽  
Ellen Goldstein ◽  
Sudarshan S. Srivats ◽  
Natalina H. Contoreggi ◽  
...  

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
I M Bahaaeldein ◽  
D A Aboubakr ◽  
N N Lasheen ◽  
N B E Soliman ◽  
M A Ahmed

Abstract Background Responses to stress could range from homeostatic variations to life-threatening effects depending on the type, timing and severity of the applied stimulus. Gender is accompanied by variations in oxidative stress, which causes the development of metabolic diseases. Under physiological conditions, females were found to be less susceptible to oxidative stress. Aim of work: This study was conducted to highlight the sex differences in the metabolic responses to chronic immobilization stress in rats, and to elucidate the possible underlying mechanisms. Materials and Methods Forty adult Wistar rats of both sexes; were randomly divided into 2 main groups: control group and stressed group, each of which was further subdivided into male and female groups. Stressed groups were exposed to chronic immobilization for 4 weeks. All rats were subjected to determination of body mass index, visceral fat weight, absolute and relative weights of liver and pancreas, plasma glucose, glucose uptake by diaphragm, glucose output by kidneys, lipid profile and plasma levels of insulin, leptin and sex hormones, malodialdehyde (MDA), total antioxidant capacity (TAC) and nitrite. HOMA-B and HOMA-IR were calculated. Also, caspase 3 was assessed in pancreas by immunohistochemistry. Results Stressed male rats showed lower BMI, higher relative liver weight, dyslipidemia, fasting hyperglycemia, higher glucose output by kidneys, lower glucose uptake by diaphragm, HOMA-B and plasma levels of insulin, testosterone and TAC and higher plasma estrogen and MDA levels compared to the control male group. Compared to the control female group, stressed female rate exhibited hyperglycemia, hypoinsulinemia, dyslipidemia, oxidative stress, higher plasma sex hormones. Compared to stressed male rats, stressed female group showed significantly higher BMI percentage change and plasma levels of TAC, estrogen and testosterone, but significantly lower absolute liver weight, glucose output by the kidneys, plasma levels of total cholesterol and triglycerides, and atherogenic index. Conclusion Chronic immobilization stress imposes greater hyperglycemic and hyperlipidemic status in males than in females. The altered sex hormonal pattern and lowered antioxidant defences could be contributory mechanisms


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