Chronic Immobilization Research Articles

Transdermal estrogen therapy in menopausal women at increased risk for thrombotic events: a scoping review.

It is estimated that over 45% of women in the United States are menopausal. Many of these women suffer from vasomotor symptoms of menopause, for which the gold standard treatment is menopause hormone therapy (MHT). However, MHT use has been controversial since the Women's Health Initiative (WHI) study in 2001. Transdermal MHT has been shown to be effective for treatment of vasomotor symptoms and does not increase the risk of venous thromboembolism (VTE) when used in healthy postmenopausal women. However, there is little data on its safety in women at increased risk for VTE such as women with prior VTE, increased body mass index, thrombophilia, tobacco use, autoimmune disease, chronic inflammatory disorders, recent surgery, trauma, or immobilization. This scoping review of the literature provides clinicians with an overview of the evidence on the risk profile of transdermal MHT use in these postmenopausal women at increased risk of VTE. We searched all published studies from 2000 to 2020 and included 13 primary articles on transdermal MHT use in postmenopausal women at increased risk of VTE. In women with prior VTE, two studies found a decrease in coagulability and no increased risk of recurrent VTE with transdermal MHT use. In women with increased body mass index, three studies found no increased VTE risk in transdermal MHT users. In women with prothrombotic genetic polymorphisms, three studies found minimal to no increased VTE risk in transdermal MHT users. In women with various proinflammatory comorbidities, five studies found an improved thrombotic profile and no increased VTE risk with transdermal MHT use. This scoping review provides data regarding the safety of transdermal MHT use in postmenopausal women with risk factors for VTE, and clinicians should have risk versus benefit discussions with each patient regarding its use.

The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context.

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

Electromagnetic stimulation facilitates spatial memory in a chronic immobilization stress model in rats

Electromagnetic stimulation facilitates spatial memory in a chronic immobilization stress model in rats

Anxiolytic effects of oxytocin in chronic immobilization stress condition are modulated by sex hormones

Anxiolytic effects of oxytocin in chronic immobilization stress condition are modulated by sex hormones

The effects of oxytocin on blood cells on the background of EMS in chronic immobilization stress model – gender differences

The effects of oxytocin on blood cells on the background of EMS in chronic immobilization stress model – gender differences

Viola tricolor Hydroalcoholic Extract Improves Behavioral Deficiencies in Rats Exposed to Chronic Immobilization Stress

HIGHLIGHTS V. tricolor ameliorates memory impairment caused by immobilization in rats. V. tricolor diminishes anxiety- and depression-like behaviors in immobilized rats. V. tricolor decreases chronic immobilization-induced neuronal loss in the hippocampus. V. tricolor reduces expression of IL-6 in the hippocampus of immobilized rats.

Involvement of the Nitricoxidergic System in the Analgesic Effects of Newly Synthesized Nociceptin Analogues After Chronic Immobilization Stress

Stress is known to exert an influence on neuroendocrine, autonomic, hormonal, and immune functioning. Various stress models have been reported to induce analgesia. This is a phenomenon referred to as stress-induced analgesia (SIA). Nociceptin and analogues are neuropeptides, neuromodulators, which are able to inhibit the expression of some forms of SIA. Nociceptin/orphanin FQ(N/OFQ) is a heptadecapeptide, which has been found to play a direct role on pain perception. Nitric oxide (NO) plays an important role in the initiation and maintenance of pain. It is also known that acute and chronic stress induce biochemical changes affecting both pain threshold and behaviour. Thus, endogenous opioid peptides and NO mediate a wide variety of physiological processes, including pain transmission and SIA. The aim of the present study was to investigate the effects of novel analogues of N/OFQ(1-13)NH 2 , where lysine (Lys) at position 9 and/or 13 was substituted by L-ornithine (Orn) on nociception after chronic immobilization stress (IS) and the involvement of the nitric oxideergic systems in these effects. Analgesic activity was examined by nociceptive test – paw-pressure (PP). All novel analogues of N/OFQ were injected at a dose of 10 μg/kg, N G -nitro-L-arginine methylester (L-NAME, 10 mg/kg) and L-arginine (L-arg, 1 mg/kg). All drugs were dissolved in saline and were injected intraperitoneally (i.p.). The nociceptive tests were performed 10 min after peptide injection. Antinociceptive effects were statistically accessed by ANOVA. In conclusion, we suggest that the nitricoxidergic system after chronic immobilization stress is involved in the analgesic effects of the novel analogues of nociceptin.

Stressed rats fail to exhibit avoidance reactions to innately aversive social calls.

Disruptions in amygdalar function, a brain area involved in encoding emotionally salient information, has been implicated in stress-related affective disorders. Earlier animal studies on the behavioral consequences of stress-induced abnormalities in the amygdala focused on learned behaviors using fear conditioning paradigms. If and how stress affects unconditioned, innate fear responses to ethologically natural aversive stimuli remains unexplored. Hence, we subjected rats to aversive ultrasonic vocalization calls emitted on one end of a linear track. Unstressed control rats exhibited a robust avoidance response by spending more time away from the source of the playback calls. Unexpectedly, prior exposure to chronic immobilization stress prevented this avoidance reaction, rather than enhancing it. Further, this stress-induced impairment extended to other innately aversive stimuli, such as white noise and electric shock in an inhibitory avoidance task. However, conditioned fear responses were enhanced by the same stress. Inactivation of the basolateral amygdala (BLA) in control rats prevented this avoidance reaction evoked by the playback. Consistent with this, analysis of the immediate early gene cFos revealed higher activity in the BLA of control, but not stressed rats, after exposure to the playback. Further, in vivo recordings in freely behaving control rats exposed to playback showed enhanced theta activity in the BLA, which also was absent in stressed rats. These findings offer a new framework for studying stress-induced alterations in amygdala-dependent maladaptive responses to more naturally threatening and emotionally relevant social stimuli. The divergent impact of stress on defensive responses--impaired avoidance responses together with increased conditioned fear--also has important implications for models of learned helplessness and depression.

Bee pollen increases hippocampal brain-derived neurotrophic factor and suppresses neuroinflammation in adult rats with chronic immobilization stress

Chronic stress is a potential problem associated with anxiety, depression, and cognitive dysfunction. Bee pollen, a powerful antioxidant, has many therapeutic effects. In this study, we aimed to examine the effects of one of the Anatolian bee pollens on depression/anxiety. 24 male Sprague Dawley rats were divided into 3 groups as control, stress, and bee pollen + stress. Bee pollen (200 mg/kg/day) was given to rats exposed to physical stress for 10 days. Open field test (OFT) and forced swimming test (FST) were applied to monitor the behavioral changes of the rats. After behavioral tests, the rats were euthanized. Brain-derived neurotrophic factor (BDNF), interleukin 1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels were measured by ELISA to evaluate neurological and biochemical changes in rat hippocampal tissue. In addition, malondialdehyde (MDA) and glutathione (GSH) levels in the brain were evaluated. According to the behavioral test results, bee pollen reduced anxiety-like behavior but did not affect depression-like behavior. We also found that bee pollen suppressed neuroinflammation while reducing oxidative stress and lipid peroxidation in hippocampal tissues. Moreover, bee pollen significantly increased the level of BDNF in the hippocampus. In conclusion, bee pollen reduced oxidative damage and neuroinflammation caused by immobilization stress in rat brain tissue. Therefore, we suggest that bee pollen may be an effective natural compound in alleviating the negative effects caused by immobilization stress.

POST-ACUTE COVID-19 SYNDROME AND DIGITAL NECROSIS: A VIRAL SEQUELAE

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus disease 2019 (COVID-19) undoubtedly produces a hypercoagulable state. Even though the pathogenesis of this phenomenon is incompletely understood, the extensive endothelial injury and elevated prothrombotic microparticles can produce clinical manifestations ranging from asymptomatic microthrombosis to death [1]. Moreover, the chronic stasis a demented and institutionalized patient has, exponentially increases the risk of embolization. CASE PRESENTATION: An 88-year-old woman with past medical history of Alzheimer's dementia, schizophrenia, paroxysmal atrial fibrillation and COVID-19 pneumonia one month prior, presented from a nursing home complaining of right hand pain. Physical examination revealed a right hand with necrosis on the tip of all five fingers and nail avulsion in the fifth digit (Figure 1, 2). The patient's apixaban had been recently discontinued due to a gastrointestinal bleed. Upon further review, no recent trauma, radiation or procedures on the right arm were noted. Initial work-up was remarkable for elevated fibrinogen activity and a D-dimer of 3350 ng/ml (reference range: less than 500). Antinuclear antibody (ANA) was positive but prothrombin time, activated partial thromboplastin time, international normalized ratio, rheumatoid factor, antineutrophil cytoplasmic antibody (ANCA), p-ANCA, C3 and C4 were within normal limits. An electrocardiogram and continuous telemetry monitoring showed normal sinus rhythm. Right hand x-ray revealed digital soft tissue swelling of the first, second and fifth digits on the right hand with no evidence of fracture (Figure 3). Ultrasound of the right upper extremity showed a non-compressible occlusive thrombus in the right cephalic vein. She was started on antibiotics while Orthopedic surgery performed partial amputation of the first and second right hand digits with debridement of the remaining fingers. Apixaban was restarted and she made a full recovery thereafter. DISCUSSION: COVID-19's dysregulated immune response inevitably leads to microvascular inflammation and cell injury. These phenomenons, in conjunction with chronic immobilization, produce a critical risk for a hypercoagulable state [1]. Furthermore, emergent research has elucidated an extensive array of manifestations in the mediate course of this viral infection. Multivariate analyses have demonstrated how the rate of venous thromboembolism in the post-acute COVID-19 patients can be up to 5% with a median of 23 days post discharge [2]. Moreover, a positive ANA without an underlying immunological disease has been described in patients with COVID-19 [3]. CONCLUSIONS: Digital necrosis should be included in potential post-COVID-19 complications and patients with high thrombosis risk must be considered for prophylactic anticoagulation. Further research is warranted to establish the potential risk-benefit relationship of treatment and the most appropriate time of prophylaxis. REFERENCE #1: Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA. 2020;324(8):799. doi:10.1001/jama.2020.13372 REFERENCE #2: Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nature Medicine. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z REFERENCE #3: Lerma LA, Chaudhary A, Bryan A, Morishima C, Wener MH, Fink SL. Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19). Journal of Translational Autoimmunity. 2020;3:100073. doi:10.1016/j.jtauto.2020.100073 DISCLOSURES: No relevant relationships by Abdul Rahman Al Armashi, source=Web Response No relevant relationships by Faris Hammad, source=Web Response No relevant relationships by Keyvan Ravakhah, source=Web Response No relevant relationships by Francisco Somoza-Cano, source=Web Response

Enriched Environment Enhances the Myelin Regulatory Factor by mTOR Signaling and Protects the Myelin Membrane Against Oxidative Damage in Rats Exposed to Chronic Immobilization Stress.

Long-term consequences of stress intervene in normal signaling of the brain leading to many psychological complications. The enriched environment (EE) may potentially ameliorate the stress response in rats. However, the mechanistic understanding of the enriched environment in protecting the myelin membrane from oxidative damage after prolonged exposure to immobilization stress (IS) remains vague. In the current study, we examined the impact of EE by exposing the rats to IS (4h/day) followed by EE treatment (2h/day) for 28 days and the activities of ROS, lipid peroxides, and phospholipids were studied, and its influence on the myelin regulatory factor (MyRF) and enzymes linked to sphingolipid was assessed in the forebrain region of myelin membrane. The ROS and lipid peroxidation was increased, and a significant decrease in the antioxidant activities was found in the IS group. IS + EE could reduce oxidative damage and increase the levels of antioxidant activities. The individual phospholipids including sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were decreased in the IS group, while IS + EE exhibited significant increase in the phospholipid classes regardless of the exposure to IS. There was down-regulation in the mRNA levels of MyRF, CERS2, SPLTC2, UGT8, and GLTP, while IS + EE could mitigate the up-regulation in the levels of mRNA of MyRF, CERS2, SPLTC2, UGT8, and GLTP. The protein expression of MOG, PLP1, and mTOR was found to be reduced in the IS group of rats, however, IS + EE revealed significant increase in the expression of these signaling molecules. These results suggest that EE had a positive effect on chronic stress response by protecting the myelin membrane against oxidative damage and increasing the protein synthesis required for myelin membrane plasticity via activation of MyRF and mTOR signaling in the forebrain region of IS exposed rats.

Differential Impact of Acute and Chronic Stress on CA1 Spatial Coding and Gamma Oscillations.

Chronic and acute stress differentially affect behavior as well as the structural integrity of the hippocampus, a key brain region involved in cognition and memory. However, it remains unclear if and how the facilitatory effects of acute stress on hippocampal information coding are disrupted as the stress becomes chronic. To examine this, we compared the impact of acute and chronic stress on neural activity in the CA1 subregion of male mice subjected to a chronic immobilization stress (CIS) paradigm. We observed that following first exposure to stress (acute stress), the spatial information encoded in the hippocampus sharpened, and the neurons became increasingly tuned to the underlying theta oscillations in the local field potential (LFP). However, following repeated exposure to the same stress (chronic stress), spatial tuning was poorer and the power of both the slow-gamma (30–50 Hz) and fast-gamma (55–90 Hz) oscillations, which correlate with excitatory inputs into the region, decreased. These results support the idea that acute and chronic stress differentially affect neural computations carried out by hippocampal circuits and suggest that acute stress may improve cognitive processing.

Ultrastructural Changes in Adrenocortical Zona Fasciculate Cells Upon Exposure to Chronic Immobilization Stress and the Ameliorating Effect of Panax Ginseng Extract

Ultrastructural Changes in Adrenocortical Zona Fasciculate Cells Upon Exposure to Chronic Immobilization Stress and the Ameliorating Effect of Panax Ginseng Extract

Inflammatory Bowel Disease and Thrombosis: A National Inpatient Sample (NIS) Study

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal mucosa, including two disorders, regional enteritis and ulcerative colitis. These disorders are characterized by defective immune regulation, in which T cells in the gastrointestinal mucosa secrete inflammatory cytokines and an inflammatory response that increases venous thromboembolism (VTE) risk, 2-3 times greater than in the general population. The mechanism by which thrombosis occurs and how to identify those at risk remain unclear.Methods: We conducted a cross-sectional analysis of discharge data from the National Inpatient Sample (NIS) between January 1, 2009 and December 31, 2014. The NIS is an all-payer database that approximates a 20% stratified sample of discharges from U.S. hospitals participating in the Healthcare Cost and Utilization Project. Discharges among individuals with and without IBD were evaluated by age, race, gender, primary and secondary diagnoses, demographics, and length of stay. De-identified discharge data were classified by the International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE); arterial thrombosis and arterial embolism; intra-abdominal thromboses, including portal vein thrombosis, splenic/other vein thrombosis, and mesenteric vein thrombosis; and other thrombosis, including cerebral artery embolism/ thrombosis, intracranial venous sinus thrombosis, retinal vein occlusion; and hepatic vein thrombosis. Discharge-level weights from the NIS database were used to produce estimates representative of all community hospitals in the U.S. Thrombosis prevalence was compared between patients with and without IBD, as were demographics (age, race, gender), length of stay, inpatient mortality, and risk factors for thrombosis (dehydration, malnutrition, ports/catheters, chronic steroid use, malignancy, surgery, trauma, and immobilization). Medical conditions i.e. hypertension, renal failure. Continuous data (e.g. age) were compared by weighted simple linear regression. Categorical data (e.g. gender and risk factors) were compared across groups by the Rao-Scott Χ2 test. Weighted multivariable logistic regression models for thrombosis were fitted to estimate odds ratios and 95% confidence intervals.Results: During the 5-year period 2009-2014, the prevalence of thrombosis in patients with IBD (unweighted N= 374,315) was 7.5%, significantly higher than in non-IBD patients (unweighted N=44,748,771), 4.5%, p<0.001. Individuals with IBD and thrombosis were older than IBD without thrombosis, 57.5 years vs. 50.4 years, p<0.001. The most common types of thrombosis were mesenteric vein thrombosis, 7.4%, PE, 6.5%, DVT 6.2%, and portal vein thrombosis, 2.5%. The most common risk factors for thrombosis included surgery, 53.7%, ports/catheters, 13.2%, malignancy, 13.1%, dehydration, 12.4%, malnutrition, 8.9%, and chronic steroid use, 8.2%, which, except dehydration, were all more common than in IBD without thrombosis, p<0.001. Hypertension, 45.2%, hyperlipidemia, 21.5%, cardiac disease, 16.6%, diabetes, 14.9% and renal failure, 13.6%, each p<0.001, were also more common in those with thrombosis. Severity of illness was higher, 1.42 vs. 0.96, length of stay longer, 7.7 vs.5.5 days, and inpatient mortality higher, 3.8% vs. 1.5%, each p<0.001. After adjusting for age and comorbidity index, risk factors remaining significant for thrombosis included port/catheters, OR=1.73 (CI 1.66,1.81), chronic steroids, OR=1.61 (1.54,1.69), malnutrition, OR=1.34 (1.28,1.41), and malignancy, OR=1.13 (1.08,1.18), each p<0.001, while dehydration, OR=0.86 (0.83,0.90), and Asian race, OR=0.61 (0.52,0.72), each p<0,001, appeared protective against thrombosis.Conclusion: This NIS analysis indicates the prevalence of thrombosis in IBD is 1.7-fold greater than in those without IBD. Even after adjusting for age and severity of illness, the odds of thrombosis in IBD are 73% higher with ports, 61% higher with chronic steroids, 34% higher with malnutrition, and 13% higher with malignancy. These findings suggest the importance of anticoagulation, particularly in IBD patients admitted with ports/catheters, steroids, malnutrition, and/or malignancy and suggest potential benefit if continued long-term in the outpatient setting. DisclosuresRagni:Shire: Consultancy, Honoraria, Research Funding; Sangamo: Research Funding; Alnylam: Consultancy, Honoraria, Research Funding; MOGAM: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Research Funding; SPARK: Research Funding; NovoNordisk: Honoraria; Bioverativ: Consultancy, Honoraria, Research Funding; Biomarin: Consultancy, Honoraria, Research Funding; Genentech/Roche: Research Funding.

Activation of 6–8-week-old new mature adult-born dentate granule cells contributes to anxiety-like behavior

Adult-born dentate granule cells (aDGCs) at 4–6 weeks of age are particularly excitable but subsequently develop the quiet properties of mature cells. Most existing studies have focused on the hyperactivity of 4–6-week-old aDGCs or neurogenesis, which confers stress resilience or buffers stress responses. However, the function of the quiet property of new mature aDGCs remains unclear. Here we used a retrovirus expressing cre recombinase in combination with an associated-adenovirus to specifically interfere with the activity of new mature aDGCs, and estimated anxiety-like behaviors by the open-field test and elevated plus maze test, antidepressant-like behaviors by the tail suspension test, and spatial memory by the Barnes maze test. We found that sustained hyperactivity of 6–8-week-old, but not 8–10-week-old, aDGCs induced anxiety-like behaviors, and suppression of the activity of 6–8-week-old aDGCs disturbed spatial memory. Meanwhile, sustained hyperactivity of 6–8-week-old aDGCs induced activation of mature dentate gyrus (DG) neurons and inhibition of immature aDGCs. Additionally, the mice showing anxiety-like behaviors induced by chronic mild immobilization stress exhibited increased activity in 6–8-week-old aDGCs. Furthermore, the sustained hyperactivity of mature DG neurons also induced anxiety-like behaviors and decreased the activity of immature aDGCs. Our results combined show that the excitation of 6–8-week-old new mature aDGCs, which prohibits them from normally entering the resting state, determines anxiety-like behavior, while the maintenance of normal excitation ability of 6–8-week-old new mature aDGCs confers memory. Our results suggests that strategies aimed at inhibiting unusual hyperactive new mature aDGCs at a restricted time window may protect against stress-related psychiatric disorders, such as anxiety and depression.

Susceptibility to chronic immobilization stress\u2010induced depressive-like behaviour in middle\u2010aged female mice and accompanying changes in dopamine D1 and GABAA receptors in related brain regions

BackgroundMiddle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. Dopaminergic and GABAergic system dysfunction is involved in the pathophysiology of depression. In the current study, we used 2-month-old and 11-month-old C57BL/6 mice as young and middle-aged mice, respectively. Chronic immobilization stress (CIS) was used to induce depressive-like behaviour, and the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess these behaviours. We then measured the mRNA levels of dopamine receptor D1 (DRD1) and the GABAA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC).ResultsWe found that immobility time in the FST was significantly increased in the middle-aged mice compared with the middle-aged control mice and the young mice. In addition, the preference for sucrose water was reduced in the middle-aged mice compared with the middle-aged control mice. However, CIS did not induce obvious changes in the performance of the young mice in our behavioural tests. Moreover, the middle-aged mice exhibited equal immobility times as the young mice in the absence of stress. Decreases in the mRNA levels of DRD1, GABRA1, and GABRB2 but not GABRG2 were found in the NAc and PFC in the middle-aged mice in the absence of stress. Further decreases in the mRNA levels of DRD1 in the NAc and GABRG2 in the NAc and PFC were found in the middle-aged mice subjected to CIS.ConclusionsOur results suggested that ageing could not directly induce depression in the absence of stress. However, ageing could induce susceptibility to depression in middle-aged mice in the presence of stress. CIS-induced decreases in DRD1 and GABRG2 levels might be involved in the increase in susceptibility to depression in this context.

FARE GEBELİK DÖNEMİNDE HAREKETSİZLİK STRESİNİN PLASENTA VE YAVRUYA ETKİLERİ

ABSTRACT AIM: Stress can affect negatively mother and fetuses during pregnancy. We aimed to investigate the effects of chronic immobilization stress on placental maturation and fetal development.MATERİALS AND METHODS: Balb/c virgin female mice (20-30 g) were mated with male mice in a 2 to 1 female to male ratio. Pregnant mice in control group (n=6) were left undisturbed, whereas pregnant mice in the stress group (n=6) were exposed to 45 min chronic immobilization stress for three times/day starting from gestational day 6 till 18. Fetuses and placentas were removed from dams on the gestational day 18 under anesthesia.RESULTS: The prenatal stress significantly increased apoptosis in several placental cells including trophoblastic giant cells, glycogen cells and labyrinth trophoblastic cells and resulted in intrauterine growth restriction. The stress caused a decreased superoxide dismutase and glutathione levels. Alizarin Red S staining shows the ossification center of the fetuses to see developmental abnormality. CONCLUSION: Gestational stress causes placental dysfunctions by triggering apoptosis, reducing the labyrinth zone as well as increasing collagen levels, which may impair fetal development that may contribute to pathogenesis of intrauterine growth restriction.

Gonadotropin levels reduced in seven days immobilization stress-induced depressive-like behavior in female rats

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. Adult Wistar albino female rats were divided into three groups as follows (n=7 for each group): control, IMO-1 (45min daily for 7-day) and IMO-2 (45min 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. 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. Our results indicated that depression-like behaviors increased, and gonadotropins decreased in the female rats exposed to 7-day chronic IMO.

Chronic stress differentially altersmRNAexpression of opioid peptides and receptors in the dorsal hippocampus of female and male rats

Chronic immobilization stress (CIS) results in sex-dependent changes in opioid peptide levels and receptor subcellular distributions within the rat dorsal hippocampus, which are paralleled with an inability for males to acquire conditioned place preference (CPP) to oxycodone. Here, RNAScope in situ hybridization was used to determine the expression of hippocampal opioid peptides and receptors in unstressed (US) and CIS estrus female and male adult (∼2.5 months old ) Sprague Dawley rats. In all groups, dentate granule cells expressed PENK and PDYN; additionally, numerous interneurons expressed PENK. OPRD1 and OPRM1 were primarily expressed in interneurons, and to a lesser extent, in pyramidal and granule cells. OPRK1-was expressed in sparsely distributed interneurons. There were few baseline sex differences: US females compared to US males had more PENK-expressing and fewer OPRD1-expressing granule cells and more OPRM1-expressing CA3b interneurons. Several expression differences emerged after CIS. Both CIS females and males compared to their US counterparts had elevated: (1) PENK-expressing dentate granule cells and interneurons in CA1 and CA2/3a; (2) OPRD1 probe number and cell expression in CA1, CA2/3a and CA3b and the dentate gyrus; and (3) OPRK1-expressing interneurons in the dentate hilus. Also, CIS males compared to US males had elevated: (1) PDYN expression in granule cells; (2) OPRD1 probe and interneuron expression in CA2/3a; (3) OPRM1 in granule cells; and (4) OPRK1 interneuron expression in CA2/3a. The sex-specific changes in hippocampal opioid gene expression may impact network properties and synaptic plasticity processes that may contribute to the attenuation of oxycodone CPP in CIS males.

Influence of progestational stress on BDNF and NMDARs in the hippocampus of male offspring and amelioration by Chaihu Shugan San

BackgroundProgestational stress has been proven to be a risk for the neural development of offspring, especially in the hippocampus. However, whether Chaihu Shugan San (CSS) can ameliorate hippocampal neural development via the regulation of brain-derived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptors (NMDAR) 2A (NR2A) and 2B (NR2B), and the mechanism of such action remains unclear. MethodsThirty-six female rats were randomly allocated into control, chronic immobilization stress (CIS) and CSS groups according to the random number table, respectively. The male offspring were fed for 21 days after birth then randomly divided into the same three groups (6 rats/group) as the female rats. Female rats, except for the control group, underwent 21-day CIS to established a progestational stress anxiety-like model which was evaluated by body weight, the elevated plus-maze (EPM) test and serum dopamine (DA) measured using an enzyme-linked immunosorbent assay (ELISA). The expression levels of estrogen receptors (ERα/ERβ) and progesterone receptor (PR) in female rat ovaries were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The hippocampal tissue in the 21-day offspring was observed by hematoxylin-eosin (HE) staining. The concentration of BDNF, NR2A, and NR2B were measured by RT-qPCR and immunohistochemistry in the CA3 and dentate gyrus (DG) regions of offsprings’ hippocampus. ResultsCompared with the female control group, significant differences in body weight, EPM test and DA concentration were observed in the CIS group, meanwhile, the concentration of ERα (P < 0.05), PR (P < 0.05) and ERβ in the ovaries were decreased. In the offsprings’ hippocampus of the CIS group, the chromatin of the nucleus was edge set and with condensed and irregular morphology nucleus, and the cytoplasm was unevenly stained with spaces around the cells, moreover, the expression levels of BDNF, NR2A, and NR2B were also declined (P < 0.05). However, Chaihu Shugan San reversed these changes, especially the BDNF in the DG region (P < 0.05), and NR2A and NR2B in the CA3 and DG region (P < 0.05). ConclusionsCSS could ameliorate the neural development of the hippocampus in offspring damaged by anxiety-like progestational stress in female rats via regulating the expression levels of ERα, ERβ, and PR in female rat ovaries and BDNF, NR2A, and NR2B in the hippocampus of their offspring.