scholarly journals Depressive-Like Behavior Induced by Long-Term Ouabain Administration Accompanied Alteration in Neuroinflammation Parameters in Rats

Author(s):  
Samira S. Valvassori ◽  
Jorge M. Aguiar-Geraldo ◽  
Taise Possamai-Della ◽  
Dayane D. da-Rosa ◽  
Samira Menegas ◽  
...  

Abstract Objective: The present study aims to investigate the effects of Lithium (Li) on manic- and depressive-like behaviors and inflammatory parameters in rats submitted to the bipolar disorder (BD) model induced by ouabain (OUA). Material and methods: Adult male rats received a single intracerebroventricular (ICV) injection of OUA or artificial cerebrospinal fluid (aCSF). On the fourth day after the ICV injection, the rats received intraperitoneal injections of saline (NaCl 0.9%) or Li (47.5 mg/kg), two times a day, for 14 days. On the seventh day after OUA injection, the locomotor activity was assessed (open field test), and on the fourteenth day, locomotion was evaluated again, which was followed by the forced swimming test to evaluate depressive-like behavior. After euthanasia, inflammatory parameters were evaluated in the frontal cortex and hippocampus. Results: After seven days of OUA administration, the animals showed a hyperactive behavior that was reversed by treatment with Li. After 14 days of ICV injections, rats exhibited a depressive behavior. Regarding the inflammatory parameters, measured after 14 days of the ICV infusions, OAU induced an increase in the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α, and cytokine-induced neutrophil chemoattractant-1. In contrast, Li treatment decreased these parameters. Conclusion: The animal model of BD induced by an OUA is able to induce neuroinflammation, which supports its construct validity for the BD research.

2015 ◽  
Vol 223 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Christina Leibrock ◽  
Michael Hierlmeier ◽  
Undine E. Lang ◽  
Florian Lang

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Shun-Guang Wei ◽  
Yang Yu ◽  
Robert B Felder

Introduction: Accumulating evidence indicates that sex differences exist in the clinical and experimental outcomes of various cardiovascular diseases. In addition to its protective effect on renin-angiotensin system activity, estrogen has an anti-inflammatory influence. The central actions of pro-inflammatory cytokines (PICs) contribute significantly to cardiovascular and autonomic dysfunction in hypertension and heart failure. In male adult rat, central administration of PICs induces substantial increases in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA), and blocking PICs reduces sympathetic excitation in experimental models of hypertension and heart failure. Whether PICs have similar central sympatho-excitatory effects in the female rat remains unknown. Hypothesis: We hypothesized that female rats may be protected from the central cardiovascular and autonomic effects of PICs. Methods: Urethane anesthetized male and female Sprague Dawley rats (10-12 weeks) underwent an intracerebrovascular (ICV) injection of the prototypical PIC tumor necrosis factor-α (TNF-α, 100 ng). BP (mmHg), HR (beats/min) and RSNA (% change) responses were continuously recorded for 4-5 hours. Results: In male rats (n=6), ICV TNF-α induced a dramatic and long-lasting increase (*p<0.001 vs. baseline) in BP (23.1 ± 2.5*), HR (82 ± 8*) and RSNA (109.5 ± 4.3 %*), that began within 20-30 mins and peaked at 90-120 mins after ICV injection. In the female rats (n=6), ICV TNF-α elicited significantly (p<0.05) smaller increases (*p<0.001 vs. baseline) in BP (14.8 ± 1.8*), HR (55 ± 6*) and RSNA (78.5 ± 6.3*), compared with the male rats. Conclusion: These data demonstrate a sex difference in the cardiovascular and sympathetic responses to centrally administered PICs. Whether the observed differences can be explained by an estrogen effect on TNF-α signaling per se or by an estrogen effect on TNF-α-induced renin-angiotensin activity remains to be determined. However, a reduced response of female rats to central inflammation may be an important contributor to sex differences in pathophysiology of hypertension and heart failure.


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095503
Author(s):  
Junhong Wang ◽  
Hua Zhang ◽  
Rui Qiao ◽  
Qinggang Ge ◽  
Shuisheng Zhang ◽  
...  

Background The roles of inflammation and hypercoagulation in predicting outcomes of coronavirus disease 2019 (COVID-19) are unclear. Methods Adult patients diagnosed with COVID-19 from 28 January 2020 to 4 March 2020 in Tongji Hospital, Wuhan were recruited. Data on related parameters were collected. Univariate analysis and multivariable binary logistic regression were used to explore predictors of critical illness and mortality. Results In total, 199 and 44 patients were enrolled in the training and testing sets, respectively. Elevated ferritin, tumor necrosis factor-α and D-dimer and decreased albumin concentration were associated with disease severity. Older age, elevated ferritin and elevated interleukin-6 were associated with 28-day mortality. The FAD-85 score, defined as age + 0.01 * ferritin +D-dimer, was used to predict risk of mortality. The sensitivity, specificity and accuracy of FAD-85 were 86.4%, 81.8% and 86.4%, respectively. A nomogram was established using age, ferritin and D-dimer to predict the risk of 28-day mortality. Conclusions Thrombo-inflammatory parameters provide key information on the severity and prognosis of COVID-19 and can be used as references for clinical treatment to correct inflammatory and coagulation abnormalities.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Stephanie Flore Djuichou Nguemnang ◽  
Eric Gonzal Tsafack ◽  
Marius Mbiantcha ◽  
Gilbert Ateufack ◽  
William Yousseu Nana ◽  
...  

Diabetic neuropathy, which affects 7 to 9% of the world’s population and that is usually accompanied by anxiety and depression, is chronic pain that results from impaired function of the central or peripheral nervous system. This study aimed at evaluating the antihypernociceptive, antiallodynic, anxiolytic, and antidepressant effects of Dissotis thollonii extracts. Diabetic neuropathy was induced by intraperitoneal injection of streptozotocin (200 mg/kg) in mice. The aqueous and ethanol extracts (250 and 500 mg/kg) were administered orally. Hyperalgesia (thermal and chemical), allodynia (mechanical and thermal), anxiety (high plus labyrinth, light-dark box, and social interaction), and depression (open field test, suspension test tail, and forced swimming test) were evaluated, and then the levels of some cytokines and growth factors were determined. The aqueous and ethanol extracts of Dissotis thollonii demonstrated significant antihypernociceptive (inhibition of hyperalgesia and allodynia), anxiolytic, and antidepressant activities in mice made diabetic by STZ. The extracts also significantly inhibited (p<0.001) the levels of TNF-α, IL-1β, and IL-6 in the blood as well as the levels of TNF-α, IL-1β, IL-6, IGF, and NGF in the sciatic nerve. This study shows that the extracts of Dissotis thollonii have antihypernociceptive and neuroprotective effects which could be linked to the inhibition of proinflammatory cytokines and growth factors in the blood and the sciatic nerve.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hao Li ◽  
Lan Sang ◽  
Xing Xia ◽  
Ruirui Zhao ◽  
Mingyue Wang ◽  
...  

Moxibustion has been widely accepted as an alternative therapy for major depressive disease (MDD). However, the efficacy of moxibustion treatment on MDD is highly variable because of its irregular operation. This study was designed to investigate how therapeutic duration and extent influence the anti-depression effect of moxibustion and the underlying mechanism involved. Rats with lipopolysaccharide-induced depression-like behavior were treated by moxibustion treatment. The anti-depression effect was determined by forced swimming test and open field test. Tryptophan (Trp) transport and its metabolism to serotonin (5-HT) and kynurenine (Kyn) were evaluated to explore the anti-depression mechanism. The results showed that moxibustion treatment could alleviate the depression-like behavior in rats. Trp transport and 5-HT generation were significantly increased, and the Trp-Kyn pathway was moderately inhibited by moxibustion. Prolonged therapy could be beneficial to the anti-depression effect by promoting the brain uptake of Trp and shifting the Trp metabolism to 5-HT. An enhanced therapeutic extent could increase 5-HT generation. In conclusion, this study determined that the anti-depression effect of moxibustion involves improved Trp transport and metabolism. The therapeutic duration benefits antidepressant effects, but the complex influence of the therapeutic extent on moxibustion efficacy requires further studies.


2019 ◽  
Vol 17 (1) ◽  
pp. 94-106 ◽  
Author(s):  
Rintaro Moroi ◽  
Katsuya Endo ◽  
Katsutoshi Yamamoto ◽  
Takeo Naito ◽  
Motoyuki Onodera ◽  
...  

2006 ◽  
Vol 49 (5) ◽  
pp. 481-486 ◽  
Author(s):  
Carmen Mannucci ◽  
Michele Tedesco ◽  
Maria Bellomo ◽  
Achille P. Caputi ◽  
Gioacchino Calapai

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Elizete De Moraes Reis ◽  
Francisco Waldomiro Schreiner Neto ◽  
Vitória Berg Cattani ◽  
Luis Ricardo Peroza ◽  
Alcindo Busanello ◽  
...  

In this study, we investigated the possible antidepressant-like effect ofI. paraguariensisin rats. Rats were treated for four weeks with an aqueous extract ofI. paraguariensisin drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours ofI. paraguariensisintake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile ofI. paraguariensisextract.I. paraguariensisreduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect ofI. paraguariensiswas observed in rats through the elevated plus-maze test. The antidepressant-like effect ofI. paraguariensiswas not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract ofI. paraguariensisdecreases the time of immobility in rats suggesting an antidepressant-like effect.


2004 ◽  
Vol 492 (1) ◽  
pp. 61-63 ◽  
Author(s):  
Paolo S D'Aquila ◽  
Francesca Panin ◽  
Gino Serra

2011 ◽  
Vol 29 (30) ◽  
pp. 4036-4044 ◽  
Author(s):  
Jan P. Deroose ◽  
Alexander M.M. Eggermont ◽  
Albertus N. van Geel ◽  
Jacobus W.A. Burger ◽  
Michael A. den Bakker ◽  
...  

PurposeBecause there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) –based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS.Patients and MethodsWe analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors.ResultsThe overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P < .001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%.ConclusionWe demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.


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