scholarly journals The Dysregulation of the Hypothalamic-pituitary-adrenal Axis in Diet-induced Prediabetic Male Sprague Dawley Rats

2020 ◽  
Author(s):  
Palesa Mosili ◽  
Bongeka Cassandra Mkhize ◽  
Phikelelani Ngubane ◽  
Ntethelelo Sibiya ◽  
Andile Khathi
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Forced Swim Test ◽  
Sprague Dawley ◽  
Hypothalamic Pituitary Adrenal ◽  
Swim Test ◽  
Stressed Group ◽  
Forced Swim ◽  
Sprague Dawley Rats ◽  
Acth Concentration

Abstract Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods: Sprague Dawley Rats were randomly divided into non-prediabetic group (NPD) and pre-diabetic group (PD) (n=6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, insulin resistance using the HOMA-IR index, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test (FST) were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were measured too. Results: Impaired glucose handling in the PD group as well as increase in corticosterone (CORT) was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed underwent the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.

scholarly journals The dysregulation of the hypothalamic-pituitary-adrenal axis in diet-induced prediabetic male Sprague Dawley rats

2020 ◽  
Author(s):  
Palesa Mosili ◽  
Bongeka Cassandra Mkhize ◽  
Phikelelani Ngubane ◽  
Ntethelelo Sibiya ◽  
Andile Khathi
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Forced Swim Test ◽  
Sprague Dawley ◽  
Hypothalamic Pituitary Adrenal ◽  
Swim Test ◽  
Stressed Group ◽  
Forced Swim ◽  
Sprague Dawley Rats ◽  
Acth Concentration

Abstract Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods: Sprague Dawley Rats were randomly divided into non-prediabetic group (NPD) and pre-diabetic group (PD) (n=6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test (FST) were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were measured too. Results: Impaired glucose handling in the PD group as well as increase in corticosterone (CORT) was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed underwent the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.

scholarly journals The dysregulation of the hypothalamic–pituitary–adrenal axis in diet-induced prediabetic male Sprague Dawley rats

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Palesa Mosili ◽  
Bongeka Cassandra Mkhize ◽  
Phikelelani Ngubane ◽  
Ntethelelo Sibiya ◽  
Andile Khathi
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Forced Swim Test ◽  
Diabetic Group ◽  
Sprague Dawley ◽  
Hypothalamic Pituitary Adrenal ◽  
Swim Test ◽  
Stressed Group ◽  
Sprague Dawley Rats ◽  
Acth Concentration

Abstract Background Altered function of the hypothalamic–pituitary–adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods Sprague Dawley Rats were randomly divided into non-pre-diabetic group (NPD) and pre-diabetic group (PD) (n = 6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were also measured. Results Impaired glucose handling in the PD group as well as increase in corticosterone was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed using the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.

Antidepressant‐like effects of quercetin in diabetic rats are independent of hypothalamic–pituitary–adrenal axis

2015 ◽  
Vol 28 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Enver Ahmet Demir ◽  
Hasan Serdar Gergerlioglu ◽  
Mehmet Oz
Keyword(s):  
Hpa Axis ◽  
Adrenocorticotropic Hormone ◽  
Experimental Diabetes ◽  
Forced Swim Test ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Hypothalamic Pituitary Adrenal ◽  
Swim Test ◽  
The Family ◽  
Pituitary Adrenal Axis

ObjectiveQuercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have benefits against diabetes and its complications. In the present study, we investigated effects of quercetin on depression-like behaviours and hypothalamic–pituitary–adrenal (HPA) axis in diabetic rats.MethodsExperimental diabetes was induced by using streptozotocin, and either 50 or 100 mg/kg quercetin was intraperitoneally administered for 21 days. Following the last treatment, animals were subjected to the forced swim test, and subsequently, the blood was obtained by cardiac puncture to measure plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels.ResultsA significant increase of the total immobile time, accompanied by a decrease in the immobility latency, which suggests a depressive status, was observed in diabetic animals that was reversed by the treatment of 50 mg/kg quercetin. However, the higher dose of quercetin (100 mg/kg) was ineffective in alleviating depression-like behaviours. The plasma concentrations of ACTH, and total- and free-CORT were not affected by both doses of quercetin.ConclusionTherefore, we concluded that the antidepressant-like effects of quercetin in diabetes are independent of the HPA axis.

Effects of prolonged exendin-4 administration on hypothalamic-pituitary-adrenal axis activity and water balance

2013 ◽  
Vol 304 (10) ◽  
pp. E1105-E1117 ◽  
Author(s):  
Manuel Gil-Lozano ◽  
Marina Romaní-Pérez ◽  
Verónica Outeiriño-Iglesias ◽  
Eva Vigo ◽  
Patricia L. Brubaker ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Hpa Axis ◽  
Stress Responses ◽  
Fold Increase ◽  
Acute Administration ◽  
Sprague Dawley ◽  
Hypothalamic Pituitary Adrenal ◽  
Sprague Dawley Rats ◽  
Glucagon Like Peptide 1 ◽  
Hpa Axis Activity

Exendin-4 (Ex-4) is a natural agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently being used as a treatment for type 2 diabetes mellitus due to its insulinotropic properties. Previous studies have revealed that acute administration of both GLP-1 and, in particular, Ex-4 potently stimulates hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, the effects of prolonged Ex-4 exposure on HPA function were explored. To this end, Sprague-Dawley rats were subjected to a daily regimen of two Ex-4 injections (5 μg/kg sc) for a minimum of 7 days. We found that subchronic Ex-4 administration produced a number of effects that resemble chronic stress situations, including hyperactivation of the HPA axis during the trough hours, disruption of glucocorticoid circadian secretion, hypertrophy of the adrenal gland, decreased adrenal gland sensitivity, impaired pituitary-adrenal stress responses, and reductions in both food intake and body weight. In addition, a threefold increase in diuresis was observed followed by a 1.5-fold increase in water intake; these latter effects were abolished by adrenalectomy. Together, these findings indicate that Ex-4 induces a profound dysregulation of HPA axis activity that may also affect renal function.

Sertraline treatment attenuates the sex differentiated behavioural stress response in the rat forced swim test

2011 ◽  
Vol 26 (S2) ◽  
pp. 802-802
Author(s):  
N. Kokras ◽  
C. Dalla ◽  
K. Antoniou ◽  
Z. Papadopoulou-Daifoti
Keyword(s):  
Sex Differences ◽  
Stress Response ◽  
Antidepressant Treatment ◽  
Forced Swim Test ◽  
Behavioural Response ◽  
Antidepressant Effect ◽  
Swim Test ◽  
Forced Swim ◽  
Female Wistar Rats ◽  
Climbing Behaviour

IntroductionSex differences have been described in depression and more recently in antidepressant response. Animal models and in particular the Forced Swim Test (FST), are widely used to investigate the behavioural response to stress and to antidepressant treatment.ObjectivesThe present study explored sex differences in the stress response during the FST and examined whether antidepressant treatment alleviates the sex-differentiated stress response.MethodsAdult male and female Wistar rats were subjected to a 15 min FST session and then treated with three injections of sertraline 10 mg/kg or vehicle at 0, 19 and 23 hours post-FST. Twenty-four hours after the first FST, they had a second 5 min FST session and their behaviour was recorded.ResultsVehicle-treated females exhibited 66% longer duration and 70% shorter latency of immobility than males, suggesting enhanced levels of despair. Sertraline did not significantly affect immobility, but exerted its antidepressant effect by elongating swimming duration in both sexes and shortening climbing behaviour in males only. In contrast, to vehicle-treated rats, no sex differences were observed in sertraline-treated rats in any of these behavioural parameters. However, sex-differences in head swinging behaviour, which is unaffected by sertraline treatment, were still observed in sertraline-treated rats.ConclusionsFemales appear more vulnerable than males to the FST, but the post-treatment organisation of FST behaviour is not sex-differentiated. Antidepressants seem to modulate the behavioural response in FST in a sex-specific way, due to sex differences in baseline FST performance. Consequently, the sex-differentiated stress response profile during FST is attenuated by antidepressant treatment.

scholarly journals Anoxia at Birth Induces Behaviorally-Relevant Changes in alpha2-Noradrenergic Receptor Binding in the Adult Rat

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Wayne G. Brake ◽  
Shakti Sharma
Keyword(s):  
Caesarean Section ◽  
Receptor Binding ◽  
Forced Swim Test ◽  
Sprague Dawley ◽  
Caesarean Birth ◽  
Swim Test ◽  
Ca1 Region ◽  
Forced Swim ◽  
Long Term Changes

Evidence suggests that Caesarean section birth in the rat, with or without an additional period of anoxia, results in long-term changes in brain catecholamine levels as well as reactivity to stress. The purpose of the present investigation was to determine whether Caesarean birth plus anoxia alters (alpha)2-noradrenergic receptor binding and sensitivity to the (alpha)2 receptor agonist, clonidine, in the Porsolt forced swim test. Sprague Dawley rat dams were decapitated and the uteruses were removed by Caesarean section. Pups were then delivered either immediately (Caesarean Only group), or were immersed in a saline bath for approximately 15 minutes (Caesarean plus Anoxia group) before delivery of the pups. A third group of animals born vaginally served as controls (Vaginally-born group). Four to five months postnatally, the expression of (alpha)2 receptors was measured by receptor autoradiography using [3H]-Rauwolscine binding. Receptor binding was increased in the area of the ventral hypothalamus and decreased in the CA1 region of the hippocampus in animals subjected to Caesarean plus Anoxia at birth. These animals also displayed a subsensitive response to the immobilizing effects of clonidine (100 micrograms/kg, i.p.) in the Porsolt forced swim test. Specifically these data show that Caesarean birth produces long-term changes in (alpha)2 receptor density and that, in animals subjected to Caesarean plus anoxia, these changes are reflected in a behavioral subsensitivity to the (alpha)2 agonist, clonidine. The findings reported here provide further experimental support for the hypothesis that birth complications may contribute to the pathophysiology of disorders such as schizophrenia that involve central catecholamine dysfunction.

Behavior of “arvalis” and “obscurus” chromosomal forms of common vole males in the forced swim test

2020 ◽  
Vol 324 (2) ◽  
pp. 252-261
Author(s):  
S.A. Sablina ◽  
I.V. Belozertseva
Keyword(s):  
Stress Response ◽  
Escape Behavior ◽  
Forced Swim Test ◽  
Stress Test ◽  
Water Environment ◽  
Common Vole ◽  
Exact Test ◽  
Swim Test ◽  
Forced Swim ◽  
D 12

To determine the difference in stress response between two chromosomal forms of a common vole, the “arvalis” and “obscurus”, the behavior of adult (6–12 months) lab-born vole males were evaluated in a forced swim test. During the test, they were carefully placed into glass cylinders (d=12 cm, h=20 cm) filled with water (h=15 cm, 24±1°C) and remained there for up to 6 min. Their behavioral patterns were video recorded and continuously monitored (Ethograph, ver. 2.7, RITEC, Russia) to document the duration of swimming and paddling (orientation), floating (immobility) and climbing (escape). Two series of experiments were performed, in May 2016 and June 2017, with independent groups: “arvalis” (N=9 each year) and “obscurus” (N=9 and 22 each year, respectively). The «arvalis» and «obscurus» significantly differed in their responses to the stress test. Over 35% of obscurus males (2 of 9 in 2016 and 9 of 22 in 2017) failed to complete the test, within 3 min these animals had to be rescued to prevent drowning (significant differences from “arvalis” according to Fisher's exact test). “Arvalis” voles displayed higher duration of escape attempts (F(1.14)=3.5; P=0.08 – for first; F(1.20)=15.6; P<0.001 – for second series of experiment), shorter duration of swimming and paddling (significantly in the first series – F(1.14)=14.3; P<0.005), and shorter duration of immobility (significantly in the second series – (F(1.20)=6.1; P<0.001). The results suggest that two chromosomal forms of common vole have major differences in stress response behavior. In the forced swim test, the “arvalis” voles are displaying higher endurance, associated with active escape behavior, when compared to “obscurus” animals. Further studies need to address their responses to other stress paradigms and to water environment, in general. The latter may play a major role in vole migration when they meet water barriers in their natural environment.

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