Application of Animal Models: From Physiology to Pathology

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Animals animals	3.0	4.2	2011	18.1 Days	CHF 2400	Submit
Cells cells	6.0	9.0	2012	16.6 Days	CHF 2700	Submit
Life life	3.2	2.7	2011	17.5 Days	CHF 2600	Submit
Veterinary Sciences vetsci	2.4	2.3	2014	19.6 Days	CHF 2600	Submit

19 pages, 4667 KiB

Open AccessArticle

Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling

by Jianhong Xia, Haiyun Wang, Zhihang Zhong and Jun Jiang

Cells 2024, 13(11), 953; https://doi.org/10.3390/cells13110953 (registering DOI) - 30 May 2024

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3, 5-biphosphate from phosphatidylinositol 3-phsphate. Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis. However, the precise molecular mechanisms underlying these effects remain a [...] Read more.

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3, 5-biphosphate from phosphatidylinositol 3-phsphate. Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis. However, the precise molecular mechanisms underlying these effects remain a topic of debate. In this study, we present findings from PIKfyve-deficient zebrafish embryos, revealing enlarged macrophages with giant vacuoles reminiscent of lysosomal storage disorders. Treatment with mTOR inhibitors or effective knockout of mTOR partially reverses these abnormalities and extend the lifespan of mutant larvae. Further in vivo and in vitro mechanistic investigations provide evidence that PIKfyve activity is essential for mTOR shutdown during early zebrafish development and in cells cultured under serum-deprived conditions. These findings underscore the critical role of PIKfyve activity in regulating mTOR signaling and suggest potential therapeutic applications of PIKfyve inhibitors for the treatment of lysosomal storage disorders. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

14 pages, 749 KiB

Open AccessArticle

A Comparative Analysis of the Cytotoxic and Vascular Activity Effects of Western Diamondback Rattlesnake (Crotalus atrox) and Eastern Diamondback Rattlesnake (Crotalus adamanteus) Venoms Using a Chick Embryo Model

by Barbora Bekešová, Vladimír Petrilla, Magdaléna Polláková, Zuzana Andrejčáková, Radoslava Vlčková, Barbara Dyba, Drahomíra Sopková, Monika Petrillová, Eva Petrovová and Jaroslav Legáth

Animals 2024, 14(11), 1634; https://doi.org/10.3390/ani14111634 - 30 May 2024

Abstract

Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating venom toxicity is essential for public health, and developing new tools allows for these effects to be studied more comprehensively. The research goals include the elucidation [...] Read more.

Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating venom toxicity is essential for public health, and developing new tools allows for these effects to be studied more comprehensively. The research goals include the elucidation of the physiological consequences of venom exposure and the assessment of toxicity using animal models. Chicken embryos serve as valuable models for assessing venom toxicity through the chick embryotoxicity screening test (CHEST) and the chick chorioallantoic membrane (CAM) assay, particularly useful for evaluating vascular impacts. C. adamanteus venom application resulted in higher embryotoxicity and morphological abnormalities, such as Siamese twins. The CAM assay demonstrated the hemorrhagic effects of venom, varying with venom type and concentration. The irritant potential of both venom types was classified as slight or moderate depending on their concentration. Additionally, acetylcholinesterase (AChE) activity was performed to receive information about organ toxicity. The results show that both venoms induced changes in the whole embryo, heart, and liver weights, but the C. adamanteus venom was identified as more toxic. Specific venom concentrations affected AChE activity in embryonic tissues. These findings underscore the embryotoxic and vasoactive properties of Crotalus venoms, providing valuable insights into their mechanisms of toxicity and potential applications in biomedicine. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

11 pages, 2552 KiB

Open AccessArticle

Transcutaneous Auricular Vagal Nerve Stimulation in Healthy Non-Sedated Horses: A Feasibility Study

by Valentina Vitale, Francesca Bindi, Ana Velloso Alvarez, María de la Cuesta-Torrado, Giulia Sala and Micaela Sgorbini

Vet. Sci. 2024, 11(6), 241; https://doi.org/10.3390/vetsci11060241 - 28 May 2024

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Abstract

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. [...] Read more.

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 μs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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15 pages, 4790 KiB

Open AccessArticle

Interaction between Chromodomain Y-like Protein and Androgen Receptor Signaling in Sertoli Cells Accounts for Spermatogenesis

by Kuo-Chung Lan, Yin-Hua Cheng, Yun-Chiao Chang, Kuo-Ting Wei, Pei-Ling Weng and Hong-Yo Kang

Cells 2024, 13(10), 851; https://doi.org/10.3390/cells13100851 - 16 May 2024

Viewed by 383

Abstract

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, [...] Read more.

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, we identified several AR-regulated genes involved in the maturation of spermatogenesis, including chromodomain Y-like protein (CDYL) and transition proteins 1 (TNP-1), that were significantly decreased in ARKO mouse testes. AR and CDYL were found to co-localize and interact in Sertoli cells. The AR–CDYL complex bound to the promoter regions of TNP1 and modulated their transcriptional activity. CDYL acts as a co-regulator of AR transactivation, and its expression is decreased in the Sertoli cells of human testes from patients with azoospermia. The androgen receptor–chromodomain Y-like protein axis plays a crucial role in regulating a network of genes essential for spermatogenesis in Sertoli cells. Disruption of this AR–CDYL regulatory axis may contribute to spermatogenic failure. These findings provide insights into novel molecular mechanisms targeting the AR–CDYL signaling pathway, which may have implications for developing new therapeutic strategies for male infertility. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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8 pages, 801 KiB

Open AccessBrief Report

Fetal Alcohol Spectrum Disorder: The Honey Bee as a Social Animal Model

by Marcelo P. Camilli, Olena M. Simko, Breanne Bevelander, Jenna M. Thebeau, Fatima Masood, Marina C. Bezerra da Silva, Muhammad Fahim Raza, Sofiia Markova, Oleksii Obshta, Midhun S. Jose, Sarah Biganski, Ivanna V. Kozii, Michael W. Zabrodski, Igor Moshynskyy, Elemir Simko and Sarah C. Wood

Life 2024, 14(4), 434; https://doi.org/10.3390/life14040434 - 25 Mar 2024

Viewed by 1376

Abstract

Animal models have been essential for advancing research of fetal alcohol spectrum disorder (FASD) in humans, but few animal species effectively replicate the behavioural and clinical signs of FASD. The honey bee (Apis mellifera) is a previously unexplored research model for [...] Read more.

Animal models have been essential for advancing research of fetal alcohol spectrum disorder (FASD) in humans, but few animal species effectively replicate the behavioural and clinical signs of FASD. The honey bee (Apis mellifera) is a previously unexplored research model for FASD that offers the distinct benefit of highly social behaviour. In this study, we chronically exposed honey bee larvae to incremental concentrations of 0, 3, 6, and 10% ethanol in the larval diet using an in vitro rearing protocol and measured developmental time and survival to adult eclosion, as well as body weight and motor activity of newly emerged adult bees. Larvae reared on 6 and 10% dietary ethanol demonstrated significant, dose-responsive delays to pupation and decreased survival and adult body weight. All ethanol-reared adults showed significantly decreased motor activity. These results suggest that honey bees may be a suitable social animal model for future FASD research. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 5197 KiB

Open AccessArticle

Aerobic Exercise Modulates Proteomic Profiles in Gastrocnemius Muscle of db/db Mice, Ameliorating Sarcopenia

by Yen-Chun Huang, Monika Renuka Sanotra, Chi-Chang Huang, Yi-Ju Hsu and Chen-Chung Liao

Life 2024, 14(3), 412; https://doi.org/10.3390/life14030412 - 20 Mar 2024

Viewed by 1162

Abstract

Type-2 diabetes mellitus (T2DM)-induced sarcopenia is intertwined with diminished insulin sensitivity and extracellular matrix (ECM) remodeling in skeletal muscle and other organs. Physical activities such as aerobic exercise play a crucial role in regulating blood glucose levels, insulin sensitivity, metabolic pathways, oxidative stress, [...] Read more.

Type-2 diabetes mellitus (T2DM)-induced sarcopenia is intertwined with diminished insulin sensitivity and extracellular matrix (ECM) remodeling in skeletal muscle and other organs. Physical activities such as aerobic exercise play a crucial role in regulating blood glucose levels, insulin sensitivity, metabolic pathways, oxidative stress, fibrosis, ECM remodeling, and muscle regeneration by modulating differentially expressed protein (DEP) levels. The objectives of our research were to investigate the effect of six weeks of aerobic exercise on the gastrocnemius and soleus muscle of db/db mice’s DEP levels compared to those of sedentary db/db mice. A total of eight db/db mice were divided into two groups (n = 4 per group), namely sedentary mice (SED) and exercise-trained mice (ET), of which the latter were subjected to six weeks of a moderate-intensity aerobic exercise intervention for five days per week. After the exercise intervention, biochemical tests, including analyses of blood glucose and HbA1c levels, were performed. Histological analysis using H & E staining on tissue was performed to compare morphological characters. Gastrocnemius and soleus muscles were dissected and processed for proteomic analysis. Data were provided and analyzed based on the DEPs using the label-free quantification (LFQ) algorithm. Functional enrichment analysis and Ingenuity Pathway Analysis (IPA) were employed as bioinformatics tools to elucidate the molecular mechanisms involved in the DEPs and disease progression. Significantly reduced blood glucose and HbA1c levels and an increased cross-sectional area (CSA) of gastrocnemius muscle fibers were seen in the ET group after the exercise interventions due to upregulations of metabolic pathways. Using proteomics data analysis, we found a significant decrease in COL1A1, COL4A2, ENG, and LAMA4 protein levels in the ET gastrocnemius, showing a significant improvement in fibrosis recovery, ECM remodeling, and muscle regeneration via the downregulation of the TGF-β signaling pathway. Upregulated metabolic pathways due to ET-regulated DEPs in the gastrocnemius indicated increased glucose metabolism, lipid metabolism, muscle regeneration, and insulin sensitivity, which play a crucial role in muscle regeneration and maintaining blood glucose and lipid levels. No significant changes were observed in the soleus muscle due to the type of exercise and muscle fiber composition. Our research suggests that engaging in six weeks of aerobic exercise may have a positive impact on the recovery of T2DM-induced sarcopenia, which might be a potential candidate for mitigation, prevention, and therapeutic treatment in the future. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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14 pages, 1420 KiB

Open AccessArticle

Preliminary Proteomic Study of the Porcine Pituitary Gland under Heat Stress

by Qiu Zhou, Yuan Gao, Yin Li, Huili Xie, Xiaoxi Liu, Yanhong Yong, Youquan Li, Zhichao Yu, Xingbin Ma and Xianghong Ju

Life 2024, 14(3), 366; https://doi.org/10.3390/life14030366 - 11 Mar 2024

Viewed by 860

Abstract

Although numerous studies have shown that the hypothalamic–pituitary–adrenal axis plays a vital role in the response to environmental stress by mediating the production of a series of hormones, the mechanism underlying these effects has not been elucidated. This study used proteomics techniques to [...] Read more.

Although numerous studies have shown that the hypothalamic–pituitary–adrenal axis plays a vital role in the response to environmental stress by mediating the production of a series of hormones, the mechanism underlying these effects has not been elucidated. This study used proteomics techniques to investigate the differentially expressed proteins (DEPs) in the pituitary glands of pigs and to elucidate the potential changes in the immune–neuroendocrine system under heat stress (HS). In total, 2517 peptides corresponding to 205 proteins were detected. A comparison of the expression patterns between HSs and healthy controls revealed 56 DEPs, of which 31 were upregulated and 25 were downregulated. Ingenuity pathway analysis (IPA) was used to reveal the subcellular characteristics, functional pathways, regulatory networks, and upstream regulators of the identified proteins. The results showed that these differentially expressed proteins were involved in intercellular communication, interactions, apoptosis, nervous system development, functions, abnormalities and other functions, and in the regulatory network. Moreover, the upstream regulators of the differentially expressed proteins were mainly transcriptional regulators, hormones, and cytokines. Thus, the functional network and pathway analyses could provide insights into the complexity and dynamics of HS–host interactions and may accelerate our understanding of the mechanisms underlying HS. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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17 pages, 6779 KiB

Open AccessArticle

Production of Proliferation- and Differentiation-Competent Porcine Myoblasts for Preclinical Studies in a Porcine Large Animal Model of Muscular Insufficiency

by Jasmin Knoll, Bastian Amend, Tanja Abruzzese, Niklas Harland, Arnulf Stenzl and Wilhelm K. Aicher

Life 2024, 14(2), 212; https://doi.org/10.3390/life14020212 - 31 Jan 2024

Viewed by 701

Abstract

Muscular insufficiency is observed in many conditions after injury, chronic inflammation, and especially in elderly populations. Causative cell therapies for muscle deficiencies are not state of the art. Animal models to study the therapy efficacy are, therefore, needed. We developed an improved protocol [...] Read more.

Muscular insufficiency is observed in many conditions after injury, chronic inflammation, and especially in elderly populations. Causative cell therapies for muscle deficiencies are not state of the art. Animal models to study the therapy efficacy are, therefore, needed. We developed an improved protocol to produce myoblasts suitable for pre-clinical muscle therapy studies in a large animal model. Myoblasts were isolated from the striated muscle, expanded by employing five different protocols, and characterized on transcript and protein expression levels to determine procedures that yielded optimized regeneration-competent myoblasts and multi-nucleated myotubes. We report that swine skeletal myoblasts proliferated well under improved conditions without signs of cellular senescence, and expressed significant levels of myogenic markers including Pax7, MyoD1, Myf5, MyoG, Des, Myf6, CD56 (p ≤ 0.05 each). Upon terminal differentiation, myoblasts ceased proliferation and generated multi-nucleated myotubes. Injection of such myoblasts into the urethral sphincter complex of pigs with sphincter muscle insufficiency yielded an enhanced functional regeneration of this muscle (81.54% of initial level) when compared to the spontaneous regeneration in the sham controls without myoblast injection (67.03% of initial level). We conclude that the optimized production of porcine myoblasts yields cells that seem suitable for preclinical studies of cell therapy in a porcine large animal model of muscle insufficiency. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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13 pages, 1821 KiB

Open AccessArticle

Development of an Alternative In Vitro Rumen Fermentation Prediction Model

by Xinjie Wang, Jianzhao Zhou, Runjie Jiang, Yuxuan Wang, Yonggen Zhang, Renbiao Wu, Xiaohui A, Haitao Du, Jiaxu Tian, Xiaoli Wei and Weizheng Shen

Animals 2024, 14(2), 289; https://doi.org/10.3390/ani14020289 - 17 Jan 2024

Viewed by 943

Abstract

The aim of this study is to identify an alternative approach for simulating the in vitro fermentation and quantifying the production of rumen methane and rumen acetic acid during the rumen fermentation process with different total mixed rations. In this experiment, dietary nutrient [...] Read more.

The aim of this study is to identify an alternative approach for simulating the in vitro fermentation and quantifying the production of rumen methane and rumen acetic acid during the rumen fermentation process with different total mixed rations. In this experiment, dietary nutrient compositions (neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), and dry matter (DM)) were selected as input parameters to establish three prediction models for rumen fermentation parameters (methane and acetic acid): an artificial neural network model, a genetic algorithm-bp model, and a support vector machine model. The research findings show that the three models had similar simulation results that aligned with the measured data trends (R² ≥ 0.83). Additionally, the root mean square errors (RMSEs) were ≤1.85 mL/g in the rumen methane model and ≤2.248 mmol/L in the rumen acetic acid model. Finally, this study also demonstrates the models’ capacity for generalization through an independent verification experiment, as they effectively predicted outcomes even when significant trial factors were manipulated. These results suggest that machine learning-based in vitro rumen models can serve as a valuable tool for quantifying rumen fermentation parameters, guiding the optimization of dietary structures for dairy cows, rapidly screening methane-reducing feed options, and enhancing feeding efficiency. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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