scholarly journals Systematic analysis of severity in a widely used cognitive depression model for mice

2019 ◽  
Vol 54 (1) ◽  
pp. 40-49
Author(s):  
Anne S Mallien ◽  
Christine Häger ◽  
Rupert Palme ◽  
Steven R Talbot ◽  
Miriam A Vogt ◽  
...  

Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human condition. Modern bioethics requires balancing scientific progress with animal welfare concerns. Therefore, scientifically based severity assessment of procedures is a prerequisite for choosing the least compromising paradigm according to the 3Rs principle. Evidence-based severity assessment in psychiatric animal models is scarce, particularly in depression research. Here, we assessed severity in a cognitive depression model by analysing indicators of stress and well-being, including physiological (body weight and corticosterone metabolite concentrations) and behavioural (nesting and burrowing behaviour) parameters. Additionally, a novel approach for objective individualised severity grading was employed using clustering of voluntary wheel running (VWR) behaviour. Exposure to the paradigm evoked a transient elevation of corticosterone, but neither affected body weight, nesting or burrowing behaviour. However, the performance in VWR was impaired after recurrent stress exposure, and the individual severity level increased, indicating that this method is more sensitive in detecting compromised welfare. Interestingly, the direct comparison to a somatic, chemically induced colitis model indicates less distress in the depression model. Further objective severity assessment studies are needed to classify the severity of psychiatric animal models in order to balance validity and welfare, reduce the stress load and thus promote refinement.

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261662
Author(s):  
Nora Weegh ◽  
Eva Zentrich ◽  
Dietmar Zechner ◽  
Birgitta Struve ◽  
Laura Wassermann ◽  
...  

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancreatic cancer model including surgical tumour induction and subsequent chemotherapeutic treatment via repeated intraperitoneal injections. Cancer cell injection into the pancreas was performed during a laparotomy under general anaesthesia. After a four-day recovery phase, mice received either drug treatment (galloflavin and metformin) or the respective vehicle substances via daily intraperitoneal injections. In addition to clinical scoring, an automated home-cage monitoring system was used to assess voluntary wheel running (VWR) behaviour as an indicator of impaired well-being. After surgery, slightly elevated clinical scores and minimal body weight reductions, but significantly decreased VWR behaviour were observed. During therapy, body weight declined in response to chemotherapy, but not after vehicle substance injection, while VWR activity was decreased in both cases. VWR behaviour differed between treatment groups and revealed altered nightly activity patterns. In summary, by monitoring VWR a high impact of repeated injections on the well-being of mice was revealed and substance effects on well-being were distinguishable. However, no differences in tumour growth between treatment groups were observed. This might be due to the severity of the procedures uncovered in this study, as exaggerated stress responses are potentially confounding factors in preclinical studies. Finally, VWR was a more sensitive indicator of impairment than clinical scoring in this model.


2021 ◽  
Author(s):  
Ann-Kristin Riedesel ◽  
Simeon O.A. Helgers ◽  
Arif Abdulbaki ◽  
Gökce Hatipoglu Majernik ◽  
Mesbah Alam ◽  
...  

Introduction Evidence-based grading of the impact of intracranial surgery on rat’s well-being is important for ethical and legal reasons. We assessed the severity of complex and repeated intracranial surgery in a 6-hydroxydopamine (6-OHDA) Parkinson’s rat model with subsequent intracranial electrode implantation, and in an intracranial tumor model with subsequent resection. Methods Stereotactic surgery was performed in adult male rats with the same general anesthesia and perioperative pain management. In the Parkinson’s model, Sprague Dawley (SD) rats received unilateral injection of 6-OHDA (n=11) or vehicle (n=7) into the medial forebrain bundle as first operation. After four weeks, neural electrodes were implanted in all rats as second operation. For tumor formation, BDIX/ UlmHanZtm (BDIX) rats (n=8) received frontocortical injection of BT4Ca cells as first operation, followed by tumor resection as second operation after one week. Multiple measures severity assessment was done two days before and four days after surgery in all rats, comprising clinical scoring, body weight and detailed behavioral screening. To include a condition with a known burden, rats with intracranial tumors were additionally assessed up to a predefined humane endpoint that has previously been classified as "moderate". Results After the first operation, only 6-OHDA injection resulted in transient elevated clinical scores, a mild long-lasting weight reduction and motor disturbances. After the second surgery, body weight was transiently reduced in all groups. All other parameters showed variable results. Principal Component Analysis showed a separation from the preoperative state driven by motor-related parameters after 6-OHDA injection, while separation after electrode implantation and more clearly after tumor resection was driven by pain-related parameters, although not reaching the level of the humane endpoint of our tumor model. Conclusion Overall, cranial surgery of different complexity only transiently and rather mildly affects rat’s well-being. Multiple measures assessment allows the differentiation of model-related motor disturbances in the Parkinson’s model from potentially pain-related conditions after tumor resection and electrode implantation.


2018 ◽  
Author(s):  
Andrew S. Fox ◽  
Regina Lapate ◽  
Alexander J. Shackman ◽  
Richard J Davidson

Emotion is a core feature of the human condition, with profound consequences for health, wealth, and wellbeing. Over the past quarter-century, improved methods for manipulating and measuring different features of emotion have yielded steady advances in our scientific understanding emotional states, traits, and disorders. Yet, it is clear that most of the work remains undone. Here, we highlight key challenges facing the field of affective sciences. Addressing these challenges will provide critical opportunities not just for understanding the mind, but also for increasing the impact of the affective sciences on public health and well-being.


Author(s):  
Deborah Carr ◽  
Vera K. Tsenkova

The body weight of U.S. adults and children has risen markedly over the past three decades. The physical health consequences of obesity are widely documented, and emerging research from the Midlife in the United States study and other large-scale surveys reveals the harmful impact of obesity on adults’ psychosocial and interpersonal well-being. This chapter synthesizes recent research on the psychosocial implications of body weight, with attention to explanatory mechanisms and subgroup differences in these patterns. A brief statistical portrait of body weight is provided, documenting rates and correlates of obesity, with a focus on race, gender, and socioeconomic status disparities. The consequences of body weight for three main outcomes are described: institutional and everyday discrimination, interpersonal relationships, and psychological well-being. The chapter concludes with a discussion of the ways that recent integrative health research on the psychosocial consequences of overweight and obesity inform our understanding of population health.


2021 ◽  
pp. 1-14
Author(s):  
Xiao Chang ◽  
Qiyong Gong ◽  
Chunbo Li ◽  
Weihua Yue ◽  
Xin Yu ◽  
...  

Abstract China accounts for 17% of the global disease burden attributable to mental, neurological and substance use disorders. As a country undergoing profound societal change, China faces growing challenges to reduce the disease burden caused by psychiatric disorders. In this review, we aim to present an overview of progress in neuroscience research and clinical services for psychiatric disorders in China during the past three decades, analysing contributing factors and potential challenges to the field development. We first review studies in the epidemiological, genetic and neuroimaging fields as examples to illustrate a growing contribution of studies from China to the neuroscience research. Next, we introduce large-scale, open-access imaging genetic cohorts and recently initiated brain banks in China as platforms to study healthy brain functions and brain disorders. Then, we show progress in clinical services, including an integration of hospital and community-based healthcare systems and early intervention schemes. We finally discuss opportunities and existing challenges: achievements in research and clinical services are indispensable to the growing funding investment and continued engagement in international collaborations. The unique aspect of traditional Chinese medicine may provide insights to develop a novel treatment for psychiatric disorders. Yet obstacles still remain to promote research quality and to provide ubiquitous clinical services to vulnerable populations. Taken together, we expect to see a sustained advancement in psychiatric research and healthcare system in China. These achievements will contribute to the global efforts to realize good physical, mental and social well-being for all individuals.


Author(s):  
Vijayalingam Thavasi Alagan ◽  
Rajesh Nakulan Vatsala ◽  
Ilavarasan Sagadevan ◽  
Vairamuthu Subbiah ◽  
Venkataramanan Ragothaman

Abstract Background An effort was made to assess the effectiveness of dietary supplementation of Ulva lactuca (U. lactuca), a seaweed and Azolla individually and in combination on different physiological parameters of Aseel chicken. A total of 40 Aseel chicks of 8 weeks old were allocated into four groups, C1 (control), T1 (Azolla alone), T2 (seaweed alone) and T3 (seaweed plus Azolla). Aseel chicks in C1 were fed with formulated grower feed alone, birds in T1 had control diet with 5% Azolla, birds in T2 had control diet with 3% U. lactuca and birds in T3 had control diet admixtured with 5% of Azolla and 3% of U. lactuca. Parameters were recorded for a continuous period of 2 months in 15 days interval. Results The growth performance was found to be significant (P ≤ 0.05) during 30 days of feed trials and highly significant (P ≤ 0.01) during 45 and 60 days of treatment. Birds in T3 had a higher body weight gain, shank length and feed conversion efficiency followed with T1 and T2 compared to C1. PCV, RBC, WBC and heterophil counts were not influenced (P ≥ 0.05) by dietary treatments. Uric acid, creatinine, AST, glucose, triglycerides and magnesium levels revealed a high significant (P ≤ 0.01) variation, and cholesterol level showed significant (P ≤ 0.05) changes during 30th and 60th day of feed trials between the control and treatment groups. Total protein, globulin, phosphorus and electrolytes like Na, K and Cl levels were not significant (P ≥ 0.05) during 30th day and were highly significant (P ≤ 0.01) during the 60th day of the trial. Conclusions It could be noted that inclusion of U. lactuca and Azolla as feed supplement in grower chicken had a better body weight gain when given in combination (U. lactuca and Azolla) rather than supplemented with the sole entity. Based on the haematological and serum biochemical analysis, the supplementation of U. lactuca and Azolla at the levels included in this trial did not pose any threat to the physiological well-being of Aseel chicken.


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 781 ◽  
Author(s):  
Katherine F. Wallis ◽  
Stepan B. Melnyk ◽  
Isabelle R. Miousse

Dietary methionine restriction is associated with improved health outcomes and an increase in lifespan in animal models. We have previously shown that an increase in dietary methionine induces alteration in the intestinal microbiome. The composition of the intestinal microbiota is a determinant of health and we, therefore, hypothesized that dietary methionine restriction would also induce changes in the murine microbiome. After one month on a methionine-restricted diet, five-month-old male and female C57BL/6 mice had decreased levels of serum methionine, without changes in body weight. We identified a decrease in the hepatic methylation status of animals fed a methionine-restricted diet compared to controls. This decrease was not associated with changes in DNA or protein methylation in the liver. In males, we saw an increase in families Bacteroidaceae and Verrucoccaceae (mostly A. mucinophila) and a decrease in Rumminococcaceae in animals fed a methionine-restricted diet compared to controls. In females, Bacteroidales family S24-7 was increased two-fold, while families Bacteroidaceae, Verrucoccaceae, Rumminococcaceae, and Rikenellaceae were decreased compared to controls. In summary, feeding a methionine-restricted diet for one month was associated with significant and sex-specific changes in the intestinal microbiome.


2013 ◽  
Vol 26 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Mousumi Tania ◽  
Md. Asaduzzaman Khan ◽  
Kun Xia

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1362
Author(s):  
Giorgio Smaldone ◽  
Stefano Capezzuto ◽  
Rosa Luisa Ambrosio ◽  
Maria Francesca Peruzy ◽  
Raffaele Marrone ◽  
...  

Water-bath stunning represents the most-applied stunning system in poultry slaughtering, but within the European Union, specific indications on electric parameters that should be used, such as voltage, are missing. The objective of this study was to evaluate the efficiency of two commercially available types of electrical equipment (A and B) on broilers with different live body weights and the influence of the tested parameters on meat quality. Experimental trials in a European Union-approved slaughterhouse were carried out using two different stunners. 6600 broilers, divided into three weight groups, were stunned applying different protocols based on the same current frequencies and intensity but different voltages. The state of unconsciousness (presence of corneal reflex and wings flapping) and post-mortem defects (pectoral hemorrhages and dark meat) were evaluated by blinded trained operators. The presence of corneal reflex and petechiae were the most reported consciousness signs and post-mortem injuries, respectively. Different weights played an important role within stunner A, registering statistical differences (p < 0.01) among groups. Considering injuries, an inverse relationship between body weight and lesions was found. The results highlighted the effectiveness of both stunning systems applying the best combination of electrical parameters considering the weight of the animal and ensuring its well-being.


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