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Advances in Animal Models in Biomedical Research, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 5922

Special Issue Editor


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Guest Editor
Department of Physiology, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, Romania
Interests: animal studies; atrial fibrillation; autonomic nervous system; cardiac arrhythmias; cardiac remodeling
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Dear Colleagues,

Preclinical studies have always represented, and will continue to represent, one of the pillars of medical progress. From William Harvey’s description of blood circulation to the elucidation of mechanisms that underly atherosclerosis, cardiac arrhythmias, or heart failure, and to the development of heart transplantation, valve replacement, or coronary artery bypass grafting, all major medical breakthroughs have relied on studies performed in laboratory animals. Whether we are talking about the elucidation of physiological or pathophysiological mechanisms, the identification of new therapeutic targets, the evaluation of the efficacy and safety of new therapeutic strategies, or simply the organ and tissue resources that they represent, animals are indisputably an invaluable resource for progress in human medicine. Unfortunately, for numerous reasons, not all results obtained in animal studies end up being confirmed in humans. Choosing the right animal species, using the adequate model, and applying a rigorous methodology and statistical tests are therefore critical in animal experimentation.

For this Special Issue, we invite both original research articles and reviews that provide readers of IJMS with novel data regarding the most relevant animal models used in biomedical research.

Prof. Dr. Alina Scridon
Guest Editor

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Keywords

  • animal experimentation
  • in vivo animal studies
  • interspecies differences
  • standardization of animal models
  • statistical analyses in animal studies

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Related Special Issue

Published Papers (7 papers)

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Research

20 pages, 3262 KiB  
Article
Investigating the Role of Cannabinoid Type 1 Receptors in Vascular Function and Remodeling in a Hypercholesterolemic Mouse Model with Low-Density Lipoprotein–Cannabinoid Type 1 Receptor Double Knockout Animals
by Zsolt Vass, Kinga Shenker-Horváth, Bálint Bányai, Kinga Nóra Vető, Viktória Török, Janka Borbála Gém, György L. Nádasy, Kinga Bernadett Kovács, Eszter Mária Horváth, Zoltán Jakus, László Hunyady, Mária Szekeres and Gabriella Dörnyei
Int. J. Mol. Sci. 2024, 25(17), 9537; https://doi.org/10.3390/ijms25179537 - 2 Sep 2024
Viewed by 829
Abstract
Hypercholesterolemia forms the background of several cardiovascular pathologies. LDL receptor-knockout (LDLR-KO) mice kept on a high-fat diet (HFD) develop high cholesterol levels and atherosclerosis (AS). Cannabinoid type 1 receptors (CB1Rs) induce vasodilation, although their role in cardiovascular pathologies is still controversial. [...] Read more.
Hypercholesterolemia forms the background of several cardiovascular pathologies. LDL receptor-knockout (LDLR-KO) mice kept on a high-fat diet (HFD) develop high cholesterol levels and atherosclerosis (AS). Cannabinoid type 1 receptors (CB1Rs) induce vasodilation, although their role in cardiovascular pathologies is still controversial. We aimed to reveal the effects of CB1Rs on vascular function and remodeling in hypercholesterolemic AS-prone LDLR-KO mice. Experiments were performed on a newly established LDLR and CB1R double-knockout (KO) mouse model, in which KO and wild-type (WT) mice were kept on an HFD or a control diet (CD) for 5 months. The vascular functions of abdominal aorta rings were tested with wire myography. The vasorelaxation effects of acetylcholine (Ach, 1 nM–1 µM) were obtained after phenylephrine precontraction, which was repeated with inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX), Nω-nitro-L-arginine (LNA), and indomethacin (INDO), respectively. Blood pressure was measured with the tail-cuff method. Immunostaining of endothelial NOS (eNOS) was carried out. An HFD significantly elevated the cholesterol levels in the LDLR-KO mice more than in the corresponding WT mice (mean values: 1039 ± 162 mg/dL vs. 91 ± 18 mg/dL), and they were not influenced by the presence of the CB1R gene. However, with the defect of the CB1R gene, damage to the Ach relaxation ability was moderated. The blood pressure was higher in the LDLR-KO mice compared to their WT counterparts (systolic/diastolic values: 110/84 ± 5.8/6.8 vs. 102/80 ± 3.3/2.5 mmHg), which was significantly elevated with an HFD (118/96 ± 1.9/2 vs. 100/77 ± 3.4/3.1 mmHg, p < 0.05) but attenuated in the CB1R-KO HFD mice. The expression of eNOS was depressed in the HFD WT mice compared to those on the CD, but it was augmented if CB1R was knocked out. This newly established double-knockout mouse model provides a tool for studying the involvement of CB1Rs in the development of hypercholesterolemia and atherosclerosis. Our results indicate that knocking out the CB1R gene significantly attenuates vascular damage in hypercholesterolemic mice. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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17 pages, 6257 KiB  
Article
The mRNA and microRNA Landscape of the Blastema Niche in Regenerating Newt Limbs
by Qi Zhang and Bin Lu
Int. J. Mol. Sci. 2024, 25(17), 9225; https://doi.org/10.3390/ijms25179225 - 25 Aug 2024
Viewed by 562
Abstract
Newts are excellent vertebrate models for investigating tissue regeneration due to their remarkable regenerative capabilities. To investigate the mRNA and microRNAs (miRNAs) profiles within the blastema niche of regenerating newt limbs, we amputated the limbs of Chinese fire belly newts (Cynops orientalis [...] Read more.
Newts are excellent vertebrate models for investigating tissue regeneration due to their remarkable regenerative capabilities. To investigate the mRNA and microRNAs (miRNAs) profiles within the blastema niche of regenerating newt limbs, we amputated the limbs of Chinese fire belly newts (Cynops orientalis) and conducted comprehensive analyses of the transcriptome and microRNA profiles at five distinct time points post-amputation (0 hours, 1 day, 5 days 10 days and 20 days). We identified 24 significantly differentially expressed (DE) genes and 20 significantly DE miRNAs. Utilizing weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment analysis, we identified four genes likely to playing crucial roles in the early stages of limb regeneration: Cemip, Rhou, Gpd2 and Pcna. Moreover, mRNA–miRNA integration analysis uncovered seven human miRNAs (miR-19b-1, miR-19b-2, miR-21-5p, miR-127-5p, miR-150-5p, miR-194-5p, and miR-210-5p) may regulate the expression of these four key genes. The temporal expression patterns of these key genes and miRNAs further validated the robustness of the identified mRNA-miRNA landscape. Our study successfully identified candidate key genes and elucidated a portion of the genetic regulatory mechanisms involved in newt limb regeneration. These findings offer valuable insights for further exploration of the intricate processes of tissue regeneration. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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6 pages, 602 KiB  
Communication
Copper Overload Increased Rat Striatal Levels of Both Dopamine and Its Main Metabolite Homovanillic Acid in Extracellular Fluid
by Antón Cruces-Sande, Pablo Garrido-Gil, Germán Sierra-Paredes, Néstor Vázquez-Agra, Álvaro Hermida-Ameijeiras, Antonio Pose-Reino, Estefanía Méndez-Álvarez and Ramón Soto-Otero
Int. J. Mol. Sci. 2024, 25(15), 8309; https://doi.org/10.3390/ijms25158309 - 30 Jul 2024
Viewed by 584
Abstract
Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for [...] Read more.
Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat’s striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl2/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson’s disease and other copper dysregulation states. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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16 pages, 5670 KiB  
Article
Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer’s Disease
by Lidia Sánchez-Puebla, Rosa de Hoz, Elena Salobrar-García, Alberto Arias-Vázquez, María González-Jiménez, Ana I. Ramírez, José A. Fernández-Albarral, José A. Matamoros, Lorena Elvira-Hurtado, Takaomi C. Saido, Takashi Saito, Carmen Nieto Vaquero, María I. Cuartero, María A. Moro, Juan J. Salazar, Inés López-Cuenca and José M. Ramírez
Int. J. Mol. Sci. 2024, 25(15), 8221; https://doi.org/10.3390/ijms25158221 - 27 Jul 2024
Viewed by 902
Abstract
In Alzheimer’s disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining [...] Read more.
In Alzheimer’s disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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14 pages, 2690 KiB  
Article
The Effects of Different Doses of Canthaxanthin in the Diet of Laying Hens on Egg Quality, Physical Characteristics, Metabolic Mechanism, and Offspring Health
by Junnan Zhang, Zhiqiong Mao, Jiangxia Zheng, Congjiao Sun and Guiyun Xu
Int. J. Mol. Sci. 2024, 25(13), 7154; https://doi.org/10.3390/ijms25137154 - 28 Jun 2024
Viewed by 545
Abstract
Currently, there is a dearth of in-depth analysis and research on the impact of canthaxanthin on the production performance, egg quality, physical characteristics, and offspring health of laying hens. Furthermore, the metabolic mechanism of cantharidin in the body remains unclear. Therefore, to solve [...] Read more.
Currently, there is a dearth of in-depth analysis and research on the impact of canthaxanthin on the production performance, egg quality, physical characteristics, and offspring health of laying hens. Furthermore, the metabolic mechanism of cantharidin in the body remains unclear. Therefore, to solve the above issues in detail, our study was conducted with a control group (C group), a low-dose canthaxanthin group (L group), and a high-dose canthaxanthin group (H group), each fed for a period of 40 days. Production performance was monitored during the experiment, in which L and H groups showed a significant increase in ADFI. Eggs were collected for quality analysis, revealing no significant differences in qualities except for yolk color (YC). The YC of the C group almost did not change, ranging from 6.08 to 6.20; however, the trend in YC change in other groups showed an initial intense increase, followed by a decrease, and eventually reached dynamic equilibrium. By detecting the content of canthaxanthin in the yolk, the YC change trend was found to be correlated with canthaxanthin levels in the yolk. The content of unsaturated fatty acid increased slightly in L and H groups. Following the incubation period, the physical characteristics and blood biochemical indices of chicks were evaluated. It was observed that the shank color of chicks in the L and H groups was significantly higher than that in the C group at birth. However, by the 35th day, there were no significant differences in shank color among the three groups. Further investigation into the metabolic mechanism involving canthaxanthin revealed that the substance underwent incomplete metabolism upon entering the body, resulting in its accumulation as well as metabolic by-product accumulation in the yolk. In summary, this study highlighted the importance of understanding canthaxanthin’s role in production performance, egg quality, and offspring health, providing valuable insights for breeders to optimize feeding strategies. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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14 pages, 3628 KiB  
Article
Antidepressant-like Effects of Chinese Quince (Chaenomeles sinensis) Fruit Based on In Vivo and Molecular Docking Studies
by Dong Wook Lim, Guijae Yoo, Yun Tai Kim and Changho Lee
Int. J. Mol. Sci. 2024, 25(11), 5838; https://doi.org/10.3390/ijms25115838 - 27 May 2024
Viewed by 689
Abstract
In this study, we examined the potential antidepressant-like effects of Chinese quince fruit extract (Chaenomeles sinensis fruit extract, CSFE) in an in vivo model induced by repeated injection of corticosterone (CORT)-induced depression. HPLC analysis determined that chlorogenic acid (CGA), neo-chlorogenic acid (neo-CGA), [...] Read more.
In this study, we examined the potential antidepressant-like effects of Chinese quince fruit extract (Chaenomeles sinensis fruit extract, CSFE) in an in vivo model induced by repeated injection of corticosterone (CORT)-induced depression. HPLC analysis determined that chlorogenic acid (CGA), neo-chlorogenic acid (neo-CGA), and rutin (RT) compounds were major constituents in CSFE. Male ICR mice (5 weeks old) were orally administered various doses (30, 100, and 300 mg/kg) of CSFE and selegiline (10 mg/kg), a monoamine oxidase B (MAO-B) inhibitor, as a positive control following daily intraperitoneal injections of CORT (40 mg/kg) for 21 days. In our results, mice treated with CSFE exhibited significant improvements in depressive-like behaviors induced by CORT. This was evidenced by reduced immobility times in the tail suspension test and forced swim test, as well as increased step-through latency times in the passive avoidance test. Indeed, mice treated with CSFE also exhibited a significant decrease in anxiety-like behaviors as measured by the elevated plus maze test. Moreover, molecular docking analysis indicated that CGA and neo-CGA from CSFE had stronger binding to the active site of MAO-B. Our results indicate that CSFE has potential antidepressant effects in a mouse model of repeated injections of CORT-induced depression. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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19 pages, 1600 KiB  
Article
The Influence of a High-Cholesterol Diet and Forced Training on Lipid Metabolism and Intestinal Microbiota in Male Wistar Rats
by Yuliya S. Sidorova, Nikita A. Petrov, Yuliya M. Markova, Alexey I. Kolobanov and Sergey N. Zorin
Int. J. Mol. Sci. 2024, 25(10), 5383; https://doi.org/10.3390/ijms25105383 - 15 May 2024
Viewed by 845
Abstract
Adequate experimental animal models play an important role in an objective assessment of the effectiveness of medicines and functional foods enriched with biologically active substances. The aim of our study was a comparative assessment of the effect of consumption of 1 or 2% [...] Read more.
Adequate experimental animal models play an important role in an objective assessment of the effectiveness of medicines and functional foods enriched with biologically active substances. The aim of our study was a comparative assessment of the effect of consumption of 1 or 2% cholesterol with and without regular (two times a week), moderate running exercise on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. In experimental rats, a response of 39 indicators (body weight, food consumption, serum biomarkers, liver composition, and changes in intestinal microbiota) was revealed. Total serum cholesterol level increased 1.8 times in animals consuming cholesterol with a simultaneous increase in low-density lipoprotein cholesterol (2 times) and decrease in high-density lipoprotein cholesterol (1.3 times) levels compared to the control animals. These animals had 1.3 times increased liver weight, almost 5 times increased triglycerides level, and more than 6 times increased cholesterol content. There was a tendency towards a decrease in triglycerides levels against the background of running exercise. The consumption of cholesterol led to a predominance of the Bacteroides family, due to a decrease in F. prausnitzii (1.2 times) and bifidobacteria (1.3 times), as well as an increase in Escherichia family (1.2 times). The running exercise did not lead to the complete normalization of microbiota. Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
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