Restraint Stress Response Research Articles

Contribution of the intra-hippocampal orexin system in the regulation of restraint stress response to pain-related behaviors in the formalin test.

Stress-induced antinociception (SIA) is due to the activation of several neural pathways and neurotransmitters that often suppress pain perception. Studies have shown that the orexin neuropeptide system is essential in pain modulation. Therefore, this study aimed to investigate the role of orexinergic receptors in the hippocampal CA1 region in modulating SIA response during the formalin test as an animal model of inflammatory pain. The orexin-1 receptor (OX1r) antagonist, SB334867, at 1, 3, 10, and 30 nmol or TCS OX2 29 as an orexin-2 receptor (OX2r) antagonist at the same doses were microinjected into the CA1 region in rats. Five minutes later, rats were exposed to restraint stress (RS) for 3 h, and pain-related behaviors were monitored in 5-min blocks for the 60-min test period in the formalin test. Results showed that applying RS for 3 h reduced pain responses in the early and late phases of the formalin test. The main findings showed that intra-CA1 injection of orexin receptor antagonists reduced the antinociception caused by stress in both phases of the formalin test. In addition, the contribution of OX2r in mediating the antinociceptive effect of stress was more prominent than that of OX1r in the early phase of the formalin test. However, in the late phase, both receptors worked similarly. Accordingly, the orexin system and its two receptors in the CA1 region of the hippocampus regulate SIA response to this animal model of pain in formalin test.

Electrocardiographic Evaluation of Acute Restraint and Cold Restraint Stress Response in Rats

Bu çalışmada, akut kısıtlama stresi ve soğuk kısıtlama stresinin sıçanlarda elektrokardiyografik (EKG) parametreler üzerindeki etkilerini araştırıldı. Toplam 18 adet 8-10 haftalık, ağırlıkları 180-220 g olan erkek Wistar albino rat üç eşit gruba (n=6/grup) ayrıldı. Kontrol grubundaki ratlara stresör uygulanmadı. Kısıtlama grubundaki ratlar 2 saat kısıtlayıcıda tutuldu. Soğuk tutma grubundaki ratlar kısıtlayıcı içinde 2 saat +4°C'de tutuldu. Sıçanlarda Televet II EKG cihazı (Kruuse, Almanya) ile ketamin ve ksilazin anestezisi altında EKG kaydı yapıldı ve derivasyonların analizinde Televet 100 programı (versiyon® 7.0.0, Kruuse, Heusenstamm, Almanya) kullanıldı. PR, QT, QRS intervalleri ve R dalgası amplitüdü analizinde gruplar arasında anlamlı fark yoktu (p >0,05). Ancak, kalp atım hızı soğuk kısıtlama grubunda kontrol grubuna (p

Epigallocatechin-3-gallate protects immunity and liver drug-metabolism function in mice loaded with restraint stress

(−)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess bio-activities. In this study, we investigated the protective effects of EGCG against restraint stress (RS)-induced liver injury and immunosuppression. EGCG (10, 20 and 40 mg/kg) was orally administered to mice daily for 7 days before modeling the restraint stress. lood, liver and broncho-alveolar lavage fluid (BALF) samples were collected and tested. We found that EGCG significantly reduced the release of stress hormones to weak restraint stress response. EGCG effectively improved hepatic damage by decreas the serum levels of alanine aminotransaminase (ALT) and aspartate transaminase (AST) in restraint-challenged mice. Furthermore, EGCG also significantly prevented the release of H2O2, NOS and 8-isoprostane, and reduced the levels of interleukin (IL)-1β, IL-2,and IL-6 restrained mice. EGCG can normal the level of cytochrome P450 (CYP450) 1A2, 2D22, 2E1 and 3A11 that induced by restraint stress., the inhibition status of T cells subsets in serum and gA in BALF were significantly relieved EGCG pretreatment. Taken together, our data suggest that EGCG possesse hepatic- and immune-protective properties against restraint stress through its anti-oxidant, anti-inflammatory and immunomodulatory activities.

Repeated restraint stress promotes hippocampal neuronal cell ciliogenesis and proliferation in mice

Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation

AimsPrevious investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic–pituitary–adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. Main methodsWe prenatally exposed Wistar rats to LPS (100μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2h restraint stress session. Immediately after the stressor, 22kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Key findingsOffspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. SignificanceOur findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation.

Modified endogenous carbon monoxide production through modulation of heme oxygenase activity alters some aspects of the cold restraint stress response in male albino rats

Multiple stimulatory and inhibitory inputs regulate the hypothalamic-pituitary-adrenal axis (HPA). Although the results of the previous studies are contradictory, it has been indicated that the carbon monoxide (CO) may play a role in the HPA regulation. The aim of the present study was to investigate the effect of modified endogenous CO production on some aspects of the cold restraint stress (CRS) response in adult male albino rats. Modification of the endogenous CO was performed by altering the heme oxygenase (HO) activity; its induction was achieved by administration of the hemin (HEM) and inhibition by administration of the zinc mesoporphyrin (ZM). We found that in both the non-stressed and stressed groups the HEM significantly decreased the plasma levels of epinephrine (EPI), adrenocorticotropic hormone (ACTH), corticosterone (B), cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). On the other hand, ZM significantly increased the adrenal EPI, norepinephrine (NE), dopamine (DA), and the plasma levels of EPI, NE, DA, ACTH, B, cholesterol, triglycerides, HDL-C, and LDL-C, as compared with control and stressed rats. The role of CO reaction to the CRS response could be clarified as an anti-stress effect. This is evidenced by the inhibitory effect of HO inducer, HEM, on the HPA axis and a consequent less hazardous metabolic profile which it produced. carbon monoxide, hemin, heme oxygenase, stress.

Maternal obesity programmes offspring development of non-alcoholic fatty pancreas disease

Background and aimsThe prevalence of pancreatic adenocarcinoma (PAC) parallels rising rates of obesity and dysmetabolism, a possible link being non-alcoholic fatty pancreas disease (NAFPD). We have recently shown that maternal obesity programmes the development of a dysmetabolic and fatty liver (non-alcoholic fatty liver disease, NAFLD) phenotype in adult offspring. Since the pancreas and liver originate from the same embryonic bud, it is plausible that maternal obesity may similarly programme the development of NAFPD. Our objective was to determine the effect of maternal obesity on development of NAFPD in offspring and ascertain contributions of the intra/extra-uterine periods. MethodsFemale C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a hypercalorific diet (16% fat, 33% sugar) for six weeks prior to mating and throughout pregnancy and lactation. Female offspring were cross-fostered for suckling to dams on the same or opposite diet to yield four groups: offspring of lean suckled by lean dams (n=6), offspring of obese suckled by obese dams (n=6), offspring of lean suckled by obese dams (n=5) and offspring of obese suckled by lean dams (n=6). All offspring were weaned onto a standard chow diet at 21days and sacrificed at 3months post-partum for tissue collection. ResultsOffspring subjected to an adverse suckling environment showed significant increases in body weight, pancreatic triglyceride content, TGF-β, collagen gene expression and SBP at rest along with an enhanced restraint stress response, indicating a dysmetabolic and NAFPD phenotype. ConclusionsDevelopmental programming is involved in the pathogenesis of NAFPD and appears to be largely dependent on an adverse extra-uterine environment.