Rodent Animal Models Research Articles

Perspective on using non-human primates in Exposome research

The physiological and pathological changes in the human body caused by environmental pressures are collectively referred to as the Exposome. Human society is facing escalating environmental pollution, leading to a rising prevalence of associated diseases, including respiratory diseases, cardiovascular diseases, neurological disorders, reproductive development disorders, among others. Vulnerable populations to the pathogenic effects of environmental pollution include those in the prenatal, infancy, and elderly stages of life. Conducting Exposome mechanistic research and proposing effective health interventions are urgent in addressing the current severe environmental pollution. In this review, we address the core issues and bottlenecks faced by current Exposome research, specifically focusing on the most toxic ultrafine nanoparticles. We summarize multiple research models being used in Exposome research. Especially, we discuss the limitations of rodent animal models in mimicking human physiopathological phenotypes, and prospect advantages and necessity of non-human primates in Exposome research based on their evolutionary relatedness, anatomical and physiological similarities to human. Finally, we declare the initiation of NHPE (Non-Human Primate Exposome) project for conducting Exposome research using non-human primates and provide insights into its feasibility and key areas of focus. SynopsisNon-human primate models hold unique advantages in human Exposome research.

Gateway to the study of the amygdala and emotion.

The study of the amygdala and its role in the processing of emotions has become a common focus in neuroscience. The modern expansion of research in this area is partly due to the discovery of a subcortical pathway for the transmission of emotional information and the experimental paradigm that was developed to study it. Groundbreaking experiments during the 90s utilized anatomical, neurophysiological, and behavioral lesion studies in a rodent animal model to uncover the neural circuitry of a simple emotional memory. These studies demonstrated the essential role of a specific monosynaptic pathway in emotional memory, using traditional tools and behavioral methods. The development of an animal model with a simple and appropriate classical conditioning paradigm made experimental investigations into the neural basis of emotion tenable and available to a generation of neuroscientists. These tools and a focus on the amygdala's neural connections and their essential role in emotional memory were a driving force in the explosion of research regarding the amygdala and emotion.

Exploring protein-protein interactions for the development of new analgesics.

The development of new analgesics has been challenging. Candidate drugs often have limited clinical utility due to side effects that arise because many drug targets are involved in signaling pathways other than pain transduction. Here, we explored the potential of targeting protein-protein interactions (PPIs) that mediate pain signaling as an approach to developing drugs to treat chronic pain. We reviewed the approaches used to identify small molecules and peptide modulators of PPIs and their ability to decrease pain-like behaviors in rodent animal models. We analyzed data from rodent and human sensory nerve tissues to build associated signaling networks and assessed both validated and potential interactions and the structures of the interacting domains that could inform the design of synthetic peptides and small molecules. This resource identifies PPIs that could be explored for the development of new analgesics, particularly between scaffolding proteins and receptors for various growth factors and neurotransmitters, as well as ion channels and other enzymes. Targeting the adaptor function of CBL by blocking interactions between its proline-rich carboxyl-terminal domain and its SH3-domain-containing protein partners, such as GRB2, could disrupt endosomal signaling induced by pain-associated growth factors. This approach would leave intact its E3-ligase functions, which are mediated by other domains and are critical for other cellular functions. This potential of PPI modulators to be more selective may mitigate side effects and improve the clinical management of pain.

Biocompatible Liquid Embolic for the Treatment of Microvascular Hemorrhage.

Persistent or recurrent bleeding from microvessels inaccessible for direct endovascular intervention is a major problem in medicine today. Here, an innovative catheter-directed liquid embolic (P-LE) is bioengineered for rapid microvessel embolization to treat small vessel hemorrhage. Tested in rodent, porcine, and canine animal models under normal and coagulopathic conditions, P-LE outperformed clinically used embolic materials in both survival and non-survival experiments, effectively occluding vessels as small as 40 microns with no signs of recanalization. P-LE occlusion is independent of the coagulation cascade, and its resistance to displacement is ≈ 8 times greater than systolic blood pressure. P-LE is also found to be biocompatible and x-ray visible and does not require polymerization or a chemical reaction to embolize. To simulate the clinical scenario, acute microvascular hemorrhage is created in the pig kidney, liver, or stomach; these are successfully treated with P-LE achieving immediate hemostasis. Furthermore, P-LE is found to be bactericidal to highly resistant patient-derived bacteria, suggesting that P-LE may also protect against infectious complications that may occur following embolization procedures. P-LE is safe, easy to use, and effective in treating -microvessel hemorrhage.

Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington disease models.

Huntington disease (HD) is a fatal neurodegenerative disease caused by a trinucleotide repeat expansion in exon 1 of the huntingtin gene (HTT) resulting in toxic gain-of-function and cell death. Despite its monogenic cause, the pathogenesis of HD is highly complex and increasing evidence indicates that, in addition to the full-length (FL) mutant HTT protein, the expanded exon 1 HTT (HTTexon1) protein that is translated from the HTT1a transcript generated by aberrant splicing is prone to aggregate and may contribute to HD pathology. This finding suggests that reducing the expression of HTT1a may achieve a greater therapeutic benefit than targeting only FL mutant HTT. Conversely, strategies that exclusively target FL HTT may not fully prevent the pathogenesis of HD. We have developed an engineered microRNA targeting the HTT exon 1 sequence (miHTT), delivered via adeno-associated virus serotype 5 (AAV5). The target sequence of miHTT is present in both FL HTT and HTT1a transcripts. Preclinical studies with AAV5-miHTT have demonstrated efficacy in several rodent and large animal models by reducing FL HTT mRNA and protein and rescuing HD-like phenotypes, and have been the rationale for phase I/II clinical studies now ongoing in the US and Europe. In the present study, we evaluated the ability of AAV5-miHTT to reduce the levels of aberrantly spliced HTT1a mRNA and the HTTexon1 protein in the brain of two mouse models of HD (heterozygous zQ175 knock-in mice and humanized Hu128/21 mice). Polyadenylated HTT1a mRNA and HTTexon1 protein were detected in the striatum and cortex of heterozygous zQ175 knock-in mice, but not in wild-type, littermate control mice. Intrastriatal administration of AAV5-miHTT resulted in dose-dependent expression of mature miHTT microRNA in cortical brain regions, accompanied by significant lowering of both FL HTT and HTT1a mRNA expression at two months post-injection. Mutant HTT and HTTexon1 protein levels were also significantly reduced in the striatum and cortex of heterozygous zQ175 knock-in at 2 months after AAV5-miHTT treatment and in humanized Hu128/21 mice 7 months post-treatment. The effects were confirmed in primary Hu128/21 neuronal cultures. These results demonstrate that AAV5-miHTT gene therapy is an effective approach to lower both FL HTT and the pathogenic HTTexon1 levels, which could potentially have an additive therapeutic benefit compared to other HTT-targeting modalities.

Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.

Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.

Nervonic acid triggered ovarian inflammation by inducing mitochondrial oxidative stress to activate NLRP3/ IL-1β pathway

IntroductionMetabolic syndrome is a serious public health concern across the globe. However, the typical metabolites and mechanisms underlying the decreased fertility related to metabolic syndrome is still elusive. ObjectivesThe aim of the present study was to explore the typical metabolites and mechanisms underlying the decreased fertility related with metabolic syndrome. MethodsUtilizing metabolomics, a comparative analysis was conducted on fatty acid compositions in various tissues of sows with high and low reproductive performance. Additionally, serum fatty acid compositions in a metabolic syndrome model (obese mice) induced by a high-fat diet (HFD) were investigated to elucidate the lipid metabolites associated with metabolic syndrome. Furthermore, the impact of nervonic acid (NA) on ovarian function was examined using rodent animal models (rats and mice). Through biological techniques such as transcriptomics, CUT&Tag, and analysis of post-translational protein modifications, the molecular mechanisms underlying NA mediated ovarian inflammation were further elucidated based on models utilizing ovarian granulosa cells from pigs, humans, and mice. Finally, validation was performed on ovaries from patients diagnosed with polycystic ovary syndrome. ResultsIn vitro, targeted serum lipidomic analysis revealed that sows with low embryo survival rates exhibited abnormal lipid metabolism characterized by abnormal accumulation of NA in the liver, ovary, and adipose tissue. Additionally, elevated NA levels trigger ovarian inflammation to cause ovarian dysfunction in both sows and rats. Mechanistically, NA induce mitochondrial oxidative stress through inhibiting respiratory chain proteins CYTB and NDFUB8 to activate NLRP3 inflammasome, which triggers procaspase-1 into active caspase-1, and convert the cytokine precursors pro-IL-1β into biologically active IL-1β in ovarian granulosa cells. Notably, we evidenced that NA promotes IL-1β activities by increasing H3K9ac modification level of IL-1β promoter regions and regulating the expression of the transcription factor AP-1. Finally, we found that the decreased expression of CerS2 in ovaries and the increased level of chemokine CXCL14 may be the cause of abnormal NA accumulation. Surprisingly, individuals with polycystic ovary syndrome, obesity, non-alcoholic fatty liver or gestational diabetes mellitus exhibit a high level of serum NA. ConclusionCollectively, our current study suggests that NA is a typical metabolite of metabolic syndrome, which strongly influences the ovarian function and embryo survival and also provides that interfering with mitochondrial ROS production is a potential strong strategy for target solving abnormal NA accumulation.

Wet‐Printed Stretchable and Strain‐Insensitive Conducting Polymer Electrodes: Facilitating In Vivo Gastric Slow Wave Mapping

AbstractWearable and implantable devices play a crucial role in clinical diagnosis, disease treatment, and fundamental research on the body's electrophysiology and biochemical processes. Conducting polymers are emerging as promising solutions to surpass the limitations of traditional metal‐based electrodes, offering enhanced conformability, and stretchability. However, current microfabrication techniques of CP electrodes have a number of limitations. In this study, a novel wet‐printing technique is developed for the fabrication of highly stretchable poly(3,4‐ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) microelectrodes. The wet‐printing, conducted in a liquid coagulation bath, has the advantages of being non‐contact, easy and fast to perform, and capable of printing low‐viscosity inks. Wet‐printing of PEDOT:PSS lines with a width of ≈20 µm is demonstrated. By adding D‐sorbitol as a plasticizer, an ultra‐high stretchability of PEDOT:PSS electrodes, of more than 720% is achieved while the electrodes remained conductive and strain‐insensitive up to high strains. The use of PEDOT:PSS wet‐printed electrode arrays for the electrophysiological recording from the stomach is demonstrated. The stretchable electrodes conformed swell to the tissue and recorded comparable electrophysiological signals to Au‐plated electrodes in porcine and rodent animal models. The wet‐printing approach to fabricating flexible and stretchable electrode arrays using low‐viscosity, conducting inks holds promise for applications in conformable electronics.

A Streamlined and Standardized Procedure for Generating High-Titer, High-Quality Adeno-Associated Virus Vectors Utilizing a Cell Factory Platform.

Preclinical gene therapy research, particularly in rodent and large animal models, necessitates the production of AAV vectors with high yield and purity. Traditional approaches in research laboratories often involve extensive use of cell culture dishes to cultivate HEK293T cells, a process that can be both laborious and problematic. Here, a unique in-house method is presented, which simplifies this process with a specific cell factory (or cell stacks, CF10) platform. An integration of polyethylene glycol/aqueous two-phase partitioning with iodixanol gradient ultracentrifugation improves both the yield and purity of the generated AAV vectors. The purity of the AAV vectors is verified through SDS-PAGE and silver staining, while the ratio of full to empty particles is determined using transmission electron microscopy (TEM). This approach offers an efficient cell factory platform for the production of AAV vectors at high yields, coupled with an improved purification method to meet the quality demands for in vivo studies.

20(S)-Protopanaxadiol Exerts Antidepressive Effects in Chronic Corticosterone-Induced Rodent Animal Models as an Activator of Brain-Type Creatine Kinase.

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) is an enzyme involved in brain energy homeostasis via the phosphocreatine-creatine kinase system. We previously identified PPD as directly bound to CK-BB and activated its activity in vitro. In this study, we explored the antidepressive effects of PPD that target CK-BB. First, we conducted time course studies on brain CK-BB, behaviors, and hippocampal structural plasticity responses to corticosterone (CORT) administration. Five weeks of CORT injection reduced CK-BB activity and protein levels and induced depression-like behaviors and hippocampal structural plasticity impairment. Next, a CK inhibitor and an adeno-associated virus-targeting CKB were used to diminish CK-BB activity or its expression in the brain. The loss of CK-BB in the brain led to depressive behaviors and morphological damage to spines in the hippocampus. Then, a polyclonal antibody against PPD was used to determine the distribution of PPD in the brain tissues. PPD was detected in the hippocampus and cortex and observed in astrocytes, neurons, and vascular endotheliocytes. Finally, different PPD doses were used in the chronic CORT-induced depression model. Treatment with a high dose of PPD significantly increased the activity and expression of CK-BB after long-term CORT injection. In addition, PPD alleviated the damage to depressive-like behaviors and structural plasticity induced by repeated CORT injection. Overall, our study revealed the critical role of CK-BB in mediating structural plasticity in CORT-induced depression and identified CK-BB as a therapeutic target for PPD, allowing us to treat stress-related mood disorders.

NeuroBus - Architecture for an Ultra-Flexible Neural Interface.

This article presents the system architecture for an implant concept called NeuroBus. Tiny distributed direct digitizing neural recorder ASICs on an ultra-flexible polyimide substrate are connected in a bus-like structure, allowing short connections between electrode and recording front-end with low wiring effort and high customizability. The small size (344 μm × 294 μm) of the ASICs and the ultraflexible substrate allow a low bending stiffness, enabling the implant to adapt to the curvature of the brain and achieving high structural biocompatibility. We introduce the architecture, the integrated building blocks, and the post-CMOS processes required to realize a NeuroBus, and we characterize the prototyped direct digitizing neural recorder front-end as well as polyimide-based ECoG brain interface. A rodent animal model is further used to validate the joint capability of the recording front-end and thin-film electrode array.

Abstract A087: Morphometric analysis of the terminal ductal lobular unit architecture in human breast

Abstract The major lactiferous ducts of the human breast branch out and ultimately end at terminal ductal lobular units (TDLUs). These glandular structures are the source of milk upon lactation, and also the most common origin of breast cancer. Despite their functional and clinical importance, the three dimensional (3D) architecture of TDLUs has remained undetermined, largely due to their absence in rodent animal models. By utilizing recent technological advances in optical tissue clearing and microscopy, we imaged the 3D structure of healthy human breast tissue to determine whether general branching patterns or cell type specific niches exist in the TDLU. Our data demonstrate that TDLUs have a consistent shape and their branch parameters are largely comparable between different TDLUs and individuals irrespective of age or parity. Simulation of TDLU branching morphogenesis in 3D by mathematical modelling suggests that evolutionarily conserved mechanisms regulate mammary gland branching in humans and mice, despite their anatomical differences. The data also demonstrate a new level of organization within the TDLU structure identifying a main branch that dominates in bifurcation events and exhibits a more duct-like keratin expression pattern. In all, our data provide the first structural insights into 3D human breast anatomy and branching, and exemplify the power of volumetric imaging in deeper understanding of human breast biology. Citation Format: Markus Peurla, Oona Paavolainen, Ella Tammelin, Suvi-Riitta Sulander, Larissa Mourao, Pia Boström, Nina Brück, Colinda LGJ Scheele, Pauliina Hartiala, Emilia Peuhu. Morphometric analysis of the terminal ductal lobular unit architecture in human breast [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A087.

RG7774 (Vicasinabin), an orally bioavailable cannabinoid receptor 2 (CB2R) agonist, decreases retinal vascular permeability, leukocyte adhesion, and ocular inflammation in animal models.

Preclinical studies suggest that cannabinoid receptor type 2 (CB2R) activation has a therapeutic effect in animal models on chronic inflammation and vascular permeability, which are key pathological features of diabetic retinopathy (DR). A novel CB2R agonist, triazolopyrimidine RG7774, was generated through lead optimization of a high-throughput screening hit. The aim of this study was to characterize the pharmacology, absorption, distribution, metabolism, elimination, and toxicity (ADMET) profile of RG7774, and to explore its potential for managing the key pathological features associated with retinal disease in rodents. The in vitro pharmacology of RG7774 was investigated for CB2R binding and receptor activation using recombinant human and mouse CB2R expression in Chinese hamster ovary cells, and endogenous CB2R expression in human Jurkat cells, and rat and mouse spleen cells. The ADMET profile was evaluated and the effects of RG7774 on retinal permeability, leukocyte adhesion, and choroidal neovascularization (CNV) were investigated in rodent models of retinal disease. Pharmacokinetic (PK) parameters and the exposure-response relationship were characterized in healthy animals and in animals with laser-induced CNV. RG7774 was found to be a potent (EC50: 2.8nM and Ki: 51.3nM), selective, and full CB2R agonist with no signs of cannabinoid receptor type 1 (CB1R) binding or activation. The ligand showed a favorable ADMET profile and exhibited systemic and ocular exposure after oral delivery. Functional potency in vitro translated from recombinant to endogenous expression systems. In vivo, orally administered RG7774 reduced retinal permeability and leukocyte adhesion in rodents with lipopolysaccharide (LPS)-induced uveitis and streptozotocin (STZ)-induced DR, and reduced lesion areas in rats with laser-induced CNV with an ED50 of 0.32mg/kg. Anatomically, RG7774 reduced the migration of retinal microglia to retinal lesions. RG7774 is a novel, highly selective, and orally bioavailable CB2R agonist, with an acceptable systemic and ocular PK profile, and beneficial effects on retinal vascular permeability, leukocyte adhesion, and ocular inflammation in rodent animal models. Results support the development of RG7774 as a potential treatment for retinal diseases with similar pathophysiologies as addressed by the animal models.

Effects of electromagnetic therapy on proprioception in a rodent animal model of rheumatoid arthritis

IntroductionThis study aimed primarily to investigate the effect of a PEMF on proprioception in terms of mechanoreceptor number and function and secondarily to assess the gait quality (sciatic function index) and arthritis severity (paw volume and body weight) in adjuvant-induced arthritis (AIA) RA model.MethodsTwenty-eight healthy adult male Wistar rats were randomly divided into 3 groups: (I) RA experimental model treated with a PEMF (10 animals), (II) positive control (10 animals), and (III) negative control (8 animals). Group I was exposed to a PEMF (0.3 mT 1 h/day for 2 weeks), while Groups II and III were placed in the same setup, except that the PEMF was turned off. The proprioceptive function [as tactile response (TR) / hopping response (HR) / forelimb placing test (FPT)], paw volume (PF), and mechanoreceptor numbers were then tested.ResultsThere was a significant preservation of mechanoreceptor numbers and proprioception in group I compared to group II, as follows: the number of Ruffini corpuscles mechanoreceptors (p = 0.007) and TR on days 9 and 14 (p = 0.002, 0.012, respectively) with no significant difference compared to group III. Also, PV decreased significantly in group I relative to group II (p = 0.01) with no significant difference for group III.ConclusionsPEMF significantly preserved proprioception receptors and function and decreased inflammation severity in the AIA-RA model.

Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways.

The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in CTGF expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research.

Transcriptome Profiling after Early Spinal Cord Injury in the Axolotl and Its Comparison with Rodent Animal Models through RNA-Seq Data Analysis.

Traumatic spinal cord injury (SCI) is a disabling condition that affects millions of people around the world. Currently, no clinical treatment can restore spinal cord function. Comparison of molecular responses in regenerating to non-regenerating vertebrates can shed light on neural restoration. The axolotl (Ambystoma mexicanum) is an amphibian that regenerates regions of the brain or spinal cord after damage. In this study, we compared the transcriptomes after SCI at acute (1-2 days after SCI) and sub-acute (6-7 days post-SCI) periods through the analysis of RNA-seq public datasets from axolotl and non-regenerating rodents. Genes related to wound healing and immune responses were upregulated in axolotls, rats, and mice after SCI; however, the immune-related processes were more prevalent in rodents. In the acute phase of SCI in the axolotl, the molecular pathways and genes associated with early development were upregulated, while processes related to neuronal function were downregulated. Importantly, the downregulation of processes related to sensorial and motor functions was observed only in rodents. This analysis also revealed that genes related to pluripotency, cytoskeleton rearrangement, and transposable elements (e.g., Sox2, Krt5, and LOC100130764) were among the most upregulated in the axolotl. Finally, gene regulatory networks in axolotls revealed the early activation of genes related to neurogenesis, including Atf3/4 and Foxa2. Immune-related processes are upregulated shortly after SCI in axolotls and rodents; however, a strong immune response is more noticeable in rodents. Genes related to early development and neurogenesis are upregulated beginning in the acute stage of SCI in axolotls, while the loss of motor and sensory functions is detected only in rodents during the sub-acute period of SCI. The approach employed in this study might be useful for designing and establishing regenerative therapies after SCI in mammals, including humans.

Chemical Induce Polycystic Ovarian Syndrome-Preclinical Animal Models

Polycystic ovarian syndrome is a complex endocrine disturbance that leads to hyperandrogenism, disruption in the functioning of the Hypothalamic-Pituitary-Ovary (HPO) axis and multiple cysts in ovaries. To understand and study different treatment approaches of polycystic ovarian syndrome, there are several chemical-induced animal models available that mimic polycystic ovarian syndrome. These animal models are designed to closely resemble the characteristic symptoms. Polycystic Ovarian Syndrome’s key characteristics are changes in gonadotropin and sex steroid hormone, ovarian morphology, and metabolic characteristics. Direct hormone-regulated animal models are frequently utilized to study PCOS. Rodent animal model is often used which aims to replicate the key feature of human PCOS. Various endocrine-disrupting chemicals also makes a major role in the development of PCOS. In order to bridge the gap between basic research and clinical application in the field of PCOS, PCOS-induced models are essential tools for improving our understanding of the illness and evaluating innovative therapies. The review discusses various animal models used to induced PCOS by various inducers such as aromatase inhibitor inducer (letrozole), androgen excess inducer (dihydrotestosterone, dehydroepiandrosterone, testosterone), estrogen-induced (estradiol valerate), antiprogesterone (mifepristone), monosodium-L-glutamate, bisphenol-A and tributyltin chloride. This article contributed to underlying the current understanding and provides you a complete review that overall covers various aspects, including the impact of chemical-induced models, which also includes changes in the morphology of ovaries, gonadotropin as well as, and alterations in the level of various sex steroid hormone profile. Additionally it explores the metabolic abnormalities caused by various chemical-inducers used to induce PCOS in animal. The objective of this review is to provide a comprehensive review about various chemical inducers which are responsible for the development of PCOS.

Behavioral, Genomic and Neurochemical Deficits Evoked by Neurotrauma in Adult Zebrafish (&lt;i&gt;Danio rerio&lt;/i&gt;)

Traumatic brain injury (TBI) is a serious biomedical problem with high prevalence and mortality risks. Understanding TBI in traditional (e.g., rodent) animal models often presents challenges due to the complexity of their brain and its limited regenerative capabilities. Here, we present novel data obtained using the zebrafish TBI model based on a stab wound of telencephalon, aiming to investigate behavioral and molecular consequences of TBI in zebrafish. Four days following the injury, adult zebrafish displayed hypolocomotion in the novel seen tank test and impaired working memory in the Y-maze test, paralleling behavioral deficits in rodent models and human TBI patients. Molecular analyses of key genes involved in the inflammatory response and cell death pathways revealed a remarkable upregulation of the interferon-stimulated gene 15 (isg15) in the injured telencephalon, a general biomarker for neuronal damage. Furthermore, noradrenaline (but not dopamine or serotonin) levels in whole-brain tissue declined following TBI, likely contributing to the observed cognitive deficits and implicating neurotransmitter dysregulation in TBI pathogenesis.

Impact of prolonged chronic social isolation stress on behavior and multifractal complexity of metabolic rate in Octodon degus

Social interaction can improve animal performance through the prevention of stress-related events, the provision of security, and the enhancement of reproductive output and survival. We investigated the effects of prolonged chronic social isolation stress on behavioral, cognitive, and physiological performance in the social, long-lived rodent Octodon degus. Degu pups were separated into two social stress treatments: control (CTRL) and chronically isolated (CI) individuals from post-natal and post-weaning until adulthood. We quantified anxiety-like behavior and cognitive performance with a battery of behavioral tests. Additionally, we measured their basal metabolic rate (BMR) and analyzed the multifractal properties of the oxygen consumption time series using Multifractal Detrended Fluctuation Analysis, a well-known method for assessing the fractal characteristics of biological signals. Our results showed that CI induced a significant increase in anxiety-like behaviors and led to a reduction in social and working memory in male degus. In addition, CI-treated degus reduced the multifractal complexity of BMR compared to CTRL, which implies a decrease in the ability to respond to environmental stressors and, as a result, an unhealthy state. In contrast, we did not observe significant effects of social stress on BMR. Multivariate analyses showed a clear separation of behavior and physiological variables into two clusters, corresponding to CI and CTRL degus. This study provides novel insights into the effects of prolonged chronic social isolation stress on behavior, cognitive performance, and metabolic complexity in this rodent animal model. To the best of our knowledge, it is the first study to integrate cognitive-behavioral performance and multifractal dynamics of a physiological signal in response to prolonged social isolation. These findings highlight the importance of social interactions for the well-being and overall performance of social animals.

42915 Topical application of INV-10000001, a first-in-class HSP47 inhibitor, attenuates hypertrophic scar in porcine and rodent animal models

42915 Topical application of INV-10000001, a first-in-class HSP47 inhibitor, attenuates hypertrophic scar in porcine and rodent animal models