scholarly journals The Benefits of Using New Tools for Behavioral Investigations in Animal Experimental Models

Author(s):  
Dragica Selakovic ◽  
Jovana Joksimovic

Abstract The animal experimental models of emotional disorders attempt to reproduce features of human psychiatric disorders in laboratory animals by correlating the physiological and behavioral changes associated with specific emotional states, the etiology of disorders, and responses on drug treatments. Animal experimental models that accurately recapitulate clinical pathology are indispensable for understanding molecular mechanisms and advancing preclinical studies. Behavioral tests on animal models have been developed over time in two directions: to enable the acquisition of as many valid behavior data as possible, and constructing experimental models and procedures that represent a parallel with certain conditions in humans. In this review we discuss more information for the new tools in behavioral investigations in animal experimental models. Here we described evoked beam-walking (EBW) test as a new test for estimation of anxiety levels. The reliability of that test was confirmed in our studies by using nandrolone decanoate (ND) and testosterone enanthate (TE) in supraphysiological doses. Also, we defined a new approach to estimation of exploratory activity by using these tests and an improvement of detectability in standard evaluation of depressive state levels. Taking into account that behavioral investigation in animal models still has to remain indispensable in conducting of preclinical studies, we assume that new tools that can be applied in this field may improve the quality of research.

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gabriela Elis Wachholz ◽  
Julia do Amaral Gomes ◽  
Juliano André Boquett ◽  
Fernanda Sales Luiz Vianna ◽  
Lavínia Schuler-Faccini ◽  
...  

Abstract Background Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models. Methods This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE’s Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular). Discussion With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability. Systematic review registration PROSPERO CRD42019157316


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ahmed Abdelrahman ◽  
Simone Kumstel ◽  
Xianbin Zhang ◽  
Marie Liebig ◽  
Edgar Heinz Uwe Wendt ◽  
...  

Abstract Ethical responsibility, legal requirements and the need to improve the quality of research create a growing interest in the welfare of laboratory animals. Judging the welfare of animals requires readout parameters, which are valid and sensitive as well as specific to assess distress after different interventions. In the present study, we evaluated the sensitivity and specificity of different non-invasive parameters (body weight change, faecal corticosterone metabolites concentration, burrowing and nesting activity) by receiver operating characteristic curves and judged the merit of a multi-parametric analysis by logistic regression. Chronic pancreatitis as well as laparotomy caused significant changes in all parameters. However, the accuracy of these parameters was different between the two animal models. In both animal models, the multi-parametric analysis relying on all the readout parameters had the highest accuracy when predicting distress. This multi-parametric analysis revealed that C57BL/6 mice during the course of chronic pancreatitis often experienced less distress than mice after laparotomy. Interestingly these data also suggest that distress does not steadily increase during chronic pancreatitis. In conclusion, combining these non-invasive methods for severity assessment represents a reliable approach to evaluate animal distress in models such as chronic pancreatitis.


2010 ◽  
pp. 633-644 ◽  
Author(s):  
Y Wang ◽  
U Wisloff ◽  
OJ Kemi

Exercise training-induced cardiac hypertrophy occurs following a program of aerobic endurance exercise training and it is considered as a physiologically beneficial adaptation. To investigate the underlying biology of physiological hypertrophy, we rely on robust experimental models of exercise training in laboratory animals that mimic the training response in humans. A number of experimental strategies have been established, such as treadmill and voluntary wheel running and swim training models that all associate with cardiac growth. These approaches have been applied to numerous animal models with various backgrounds. However, important differences exist between these experimental approaches, which may affect the interpretation of the results. Here, we review the various approaches that have been used to experimentally study exercise training-induced cardiac hypertrophy; including the advantages and disadvantages of the various models.


Author(s):  
David Baglietto-Vargas ◽  
Rahasson R. Ager ◽  
Rodrigo Medeiros ◽  
Frank M. LaFerla

The incidence and prevalence of neurodegenerative disorders (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), etc.) are growing rapidly due to increasing life expectancy. Researchers over the past two decades have focused their efforts on the development of animal models to dissect the molecular mechanisms underlying neurodegenerative disorders. Existing models, however, do not fully replicate the symptomatic and pathological features of human diseases. This chapter focuses on animal models of AD, as this disorder is the most prevalent of the brain degenerative conditions afflicting society. In particular, it briefly discusses the current leading animal models, the translational relevance of the preclinical studies using such models, and the limitations and shortcomings of using animals to model human disease. It concludes with a discussion of potential means to improve future models to better recapitulate human conditions.


2020 ◽  
Vol 21 (19) ◽  
pp. 7173
Author(s):  
Kwang H. Choi ◽  
Rina Y. Berman ◽  
Michael Zhang ◽  
Haley F. Spencer ◽  
Kennett D. Radford

Ketamine, a multimodal anesthetic drug, has become increasingly popular in the treatment of pain following traumatic injury as well as treatment-resistant major depressive disorders. However, the psychological impact of this dissociative medication on the development of stress-related disorders such as post-traumatic stress disorder (PTSD) remains controversial. To address these concerns, preclinical studies have investigated the effects of ketamine administration on fear memory and stress-related behaviors in laboratory animals. Despite a well-documented line of research examining the effects of ketamine on fear memory, there is a lack of literature reviews on this important topic. Therefore, this review article summarizes the current preclinical literature on ketamine and fear memory with a particular emphasis on the route, dose, and timing of ketamine administration in rodent fear conditioning studies. Additionally, this review describes the molecular mechanisms by which ketamine may impact fear memory and stress-related behaviors. Overall, findings from previous studies are inconsistent in that fear memory may be increased, decreased, or unaltered following ketamine administration in rodents. These conflicting results can be explained by factors such as the route, dose, and timing of ketamine administration; the interaction between ketamine and stress; and individual variability in the rodent response to ketamine. This review also recommends that future preclinical studies utilize a clinically relevant route of administration and account for biological sex differences to improve translation between preclinical and clinical investigations.


2021 ◽  
Vol 20 (4) ◽  
Author(s):  
Norhamidar Ab Hamid ◽  
Norsuhana Omar ◽  
Che Aishah Nazariah Ismail ◽  
Idris Long

Diabetic neuropathy (DN) is a common chronic microvascular complication of diabetes mellitus. The features of DN include allodynia, hyperalgesia, abnormal or loss of sensation of nerve fibers. The clinical features will contribute to poor quality of life, disrupt sleep, lead to depression, and increases mortality. Current drug treatments have been shown to alleviate the symptoms of DN but failed to treat the underlying causes of DN. Therefore, a better understanding of the molecular mechanisms underlying the development and progression of DN is needed for early diagnosis and intervention and understanding the failure of existing treatments. Identification of potential mechanisms is critical for better prediction of progression and for designing preventive therapies. DN's exact pathogenesis is incomplete, although it is understood that its multifunctional dysfunction involving many signaling pathways. This review summarized the common deterioration of signaling pathways and mechanisms involved in DN pathogenesis. 


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 214
Author(s):  
Ahmed Kandeil ◽  
Ahmed Mostafa ◽  
Rehab R. Hegazy ◽  
Rabeh El-Shesheny ◽  
Ahmed El Taweel ◽  
...  

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world’s population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Richard McCarty ◽  
Travis Josephs ◽  
Oleg Kovtun ◽  
Sandra J. Rosenthal

AbstractBipolar disorders (BDs) exhibit high heritability and symptoms typically first occur during late adolescence or early adulthood. Affected individuals may experience alternating bouts of mania/hypomania and depression, with euthymic periods of varying lengths interspersed between these extremes of mood. Clinical research studies have consistently demonstrated that BD patients have disturbances in circadian and seasonal rhythms, even when they are free of symptoms. In addition, some BD patients display seasonal patterns in the occurrence of manic/hypomanic and depressive episodes as well as the time of year when symptoms initially occur. Finally, the age of onset of BD symptoms is strongly influenced by the distance one lives from the equator. With few exceptions, animal models useful in the study of BD have not capitalized on these clinical findings regarding seasonal patterns in BD to explore molecular mechanisms associated with the expression of mania- and depression-like behaviors in laboratory animals. In particular, animal models would be especially useful in studying how rates of change in photoperiod that occur during early spring and fall interact with risk genes to increase the occurrence of mania- and depression-like phenotypes, respectively. Another unanswered question relates to the ways in which seasonally relevant changes in photoperiod affect responses to acute and chronic stressors in animal models. Going forward, we suggest ways in which translational research with animal models of BD could be strengthened through carefully controlled manipulations of photoperiod to enhance our understanding of mechanisms underlying seasonal patterns of BD symptoms in humans. In addition, we emphasize the value of incorporating diurnal rodent species as more appropriate animal models to study the effects of seasonal changes in light on symptoms of depression and mania that are characteristic of BD in humans.


2020 ◽  
Vol 21 (2) ◽  
pp. 533 ◽  
Author(s):  
Jeong-Im Hong ◽  
In Young Park ◽  
Hyun Ah Kim

Arthritis, including osteoarthritis (OA) and rheumatoid arthritis (RA), is the leading cause of years lived with disability (YLD) worldwide. Although pain is the cardinal symptom of arthritis, which is directly related to function and quality of life, the elucidation of the mechanism underlying the pathogenesis of pain in arthritis has lagged behind other areas, such as inflammation control and regulation of autoimmunity. The lack of therapeutics for optimal pain management is partially responsible for the current epidemic of opioid and narcotic abuse. Recent advances in animal experimentation and molecular biology have led to significant progress in our understanding of arthritis pain. Despite the inherent problems in the extrapolation of data gained from animal pain studies to arthritis in human patients, the critical assessment of molecular mediators and translational studies would help to define the relevance of novel therapeutic targets for the treatment of arthritis pain. This review discusses biological and molecular mechanisms underlying the pathogenesis of arthritis pain determined in animal models of OA and RA, along with the methodologies used.


2020 ◽  
Vol 21 (10) ◽  
pp. 3696 ◽  
Author(s):  
Deyanira Contartese ◽  
Matilde Tschon ◽  
Monica De Mattei ◽  
Milena Fini

Osteoarthritis (OA) is a highly prevalent joint disease that primarily affects about 10% of the world’s population over 60 years old. The purpose of this study is to systematically review the preclinical studies regarding sex differences in OA, with particular attention to the molecular aspect and gene expression, but also to the histopathological aspects. Three databases (PubMed, Scopus, and Web of Knowledge) were screened for eligible studies. In vitro and in vivo papers written in English, published in the last 11 years (2009–2020) were eligible. Participants were preclinical studies, including cell cultures and animal models of OA, evaluating sex differences. Independent extraction of articles and quality assessments were performed by two authors using predefined data fields and specific tools (Animals in Research Reporting In Vivo Experiments (ARRIVE) guideline and Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool). Twenty-three studies were included in the review: 4 in vitro studies, 18 in vivo studies, and 1 both in vitro and in vivo study. From in vitro works, sex differences were found in the gene expression of inflammatory molecules, hormonal receptors, and in responsiveness to hormonal stimulation. In vivo research showed a great heterogeneity of animal models mainly focused on the histopathological aspects rather than on the analysis of sex-related molecular mechanisms. This review highlights that many gaps in knowledge still exist; improvementsin the selection and reporting of animal models, the use of advanced in vitro models, and multiomics analyses might contribute to developing a personalized gender-based medicine.


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