Rodent Strains Research Articles

Interactions of pain and opioids on conditioned place preference in rodents.

Opioid analgesics are the most effective medications used for the treatment of pain, however there are significant risks associated with repeated opioid use including opioid misuse and opioid use disorder development. Chronic pain affects millions of adults in the United States, and opioid misuse is often comorbid with pain conditions in individuals who are repeatedly treated with opioids. In addition to providing pain relief, opioids produce rewarding effects, but in chronic pain states, reward processing can become dysregulated. The conditioned place preference task is commonly used to measure the rewarding properties of opioids in rodents. During this task, opioid administration is paired with a distinct environment through repeated conditioning and the change in an animal's preference for the paired environment indicates whether the opioid is rewarding or not. Rodent pain models can be combined with conditioned place preference to examine the effects of pain on opioid reward. The existing preclinical literature on pain effects on conditioned place preference is conflicting, where pain conditions have been reported to enhance, suppress, or have no effect on opioid reward. This review will discuss several factors that may contribute to these discordant findings including conditioning session duration and number, rodent strain differences in opioid sensitivity, analgesic properties of opioids at tested doses, locomotor effects at tested doses, and diurnal variation in pain sensitivity. Future studies should consider how these factors contribute to opioid conditioned place preference in both pain and pain-free animals to have a better understanding of the interactions between pain and opioid reward.

Stress-Induced Ultrasonic Vocalization in Laboratory Rats and Mice: A Scoping Review.

Introduction: Ultrasonic vocalization (USV) can indicate affective states-including psychosocial stress-in mice and rats. However, stress-induced USV changes could be confounded by laboratory experimental variables such as the type of behavioral stress paradigm, the elicitation method, rodent strain, etc. We sought to provide a review of the current literature to delineate how psychosocial stress-altered rodent USVs may be affected by factors of age, sex, strain, species, elicitation paradigm, and stressor. Methods: We used PubMed, Scopus (Elsevier), PsycINFO (EBSCO), and the following Web of Science (Clarivate) databases: Biological Abstracts, CAB Abstracts, Science Citation Index-Expanded, and Emerging Sources Citation Index. The studies identified by our search strategy were independently screened by two authors with the following inclusion criteria: peer-reviewed, in English, reported original data, and described USV in response to stress in rats or mice. The data extracted included USV acoustic parameters (mean peak frequency and mean amplitude (loudness)), details of the stress and USV elicitation paradigms, rodent species, age, and sex variables. Results: The following screening of 5309 titles/abstracts and 687 full-text articles revealed 148 articles. Footshock (20%), cold exposure (14%), and maternal separation (23.5%) were the most commonly used stress paradigms (duration and type of stressor varied across studies), with the total number of USV calls being the most commonly reported acoustic outcome. In rats, 121 articles described stress-altered USVs, while 25 studies reported the same in mice, and two reported multiple rodent species (rats and mice, alongside other rodent species such as gerbils). With respect to stress-altered USV changes with age, mice and rats increase USV rates after birth, with a peak around 6 to 10 days, and decrease USVs until weanling age. Of the five studies that reported sex-related differences in stress-induced USVs, females had an increased number of calls and lower average peak frequency in response to stress when compared to males. Only two to four studies reported strain-related differences in stress-induced vocalizations in rats and mice, respectively. Conclusions: The data from this review lay the groundwork for better understanding rodent USVs in response to psychosocial stress with effects of elicitation paradigm, stressor, age, and sex.

Prevalence and Genetic Diversity of Bat Hepatitis B Viruses in Bat Species Living in Gabon.

Hepatitis B virus (HBV) infection leads to around 800,000 deaths yearly and is considered to be a major public health problem worldwide. However, HBV origins remain poorly understood. Here, we looked for bat HBV (BtHBV) in different bat species in Gabon to investigate the role of these animals as carriers of ancestral hepadnaviruses because these viruses are much more diverse in bats than in other host species. DNA was extracted from 859 bat livers belonging to 11 species collected in caves and villages in the southeast of Gabon and analyzed using PCRs targeting the surface gene. Positive samples were sequenced using the Sanger method. BtHBV DNA was detected in 64 (7.4%) individuals belonging to eight species mainly collected in caves. Thirty-six (36) sequences among the 37 obtained after sequencing were phylogenetically close to the RBHBV strain recently isolated in Gabonese bats, while the remaining sequence was close to a rodent HBV strain isolated in America. The generalized linear mixed model showed that the variable species best explained the occurrence of BtHBV infection in bats. The discovery of a BtHBV strain homologous to a rodent strain in bats raises the possibility that these animals may be carriers of ancestral hepadnaviruses.

Abstract 2592: New technologies and capabilities supporting the development of novel molecular radiotherapy agents

Abstract At Oncodesign-Services we aim to provide cutting-edge technologies and products to support the development of radiopharmaceuticals for theranostics. Starting from the optimization of lead compounds, the site-specific bioconjugation chemistry of a bifunctional chelator to large biological compounds, such as antibodies, can preserve the biological profile and the reliable batch production. Thanks to new technologies we can conjugate a variety of payloads (cytotoxins, radioactive chelates, fluorescent dyes) on antibodies at targeted lysine residues of the Fc region, independent of Fc glycosylation. Moreover, we aim to use relevant models for valuable translational results. In line with this, we established tumor spheroids to finely monitor the diffusion and subcellular distribution of novel fluorescent and radioactive probes in a 3D environment. Furthermore, we are currently generating two animal tumor models for optimal target expression levels and recapitulation of the human tumor microenvironment. Our first model is a PSMA+ expressing tumour model, in a non radiosensitive rodent strain allowing improved assessment of novel radiopharmaceuticals. Our second tumor model is under development to assess novel FAPI tracers. Finally, we present in partnership with ImaginAb 89Zr Crefmirlimab Berdoxam​, a minibody (human and murine analog) with high affinity to the CD8α glycoprotein, a valuable PET imaging tool for preclinical tracking and assessment of CD8 cells. This PET imaging can be used to evaluate immunoresponse following treatment, autoimmune, inflammatory and/or infectious diseases models. To conclude, our continuous efforts aim at expanding our service portfolio to fulfil the needs of our various projects, as presented herein. Our experience and expertise allow us to suggest alternatives based on the latest technological progresses to facilitate and expedite the drug discovery progress from bench to bedside. Citation Format: Sarah Belderbos, Celine Mothes, Claire Bernhard, Franck Denat, Pierre Adumeau, Merari Tumin Chevalier, Jordi Llop, Agnieszka Kownacka, Calmen Tihansky, Marie Ruch, Michael Claron, Mathieu Moreau, Cyril Berthet, Eftychia Koumarianou. New technologies and capabilities supporting the development of novel molecular radiotherapy agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2592.

MAT gene deregulation and liver cancer

Rodent models with low heterogeneity premalignant and malignant lesions provide a valuable contribution to hepatocellular carcinoma (HCC) pathogenesis in the field of research. Studies have been performed in transgenic mice, and rodent strains on signaling pathways deregulation in hepatocarcinogenesis with varying susceptibilities, and human HCC subtypes. Because ethionine, an antagonist of methionine, causes cancer and methyl-deficient diets cause steatohepatitis, followed by the development of HCC, researchers began to look into mechanisms regulating availability of S-adenosylmethionine (SAM) and its role in liver injury, including HCC development. Cirrhotic livers have decreased methionine adenosyltransferase (MATI/III) levels due to oxidation of cysteine residues in the ATP-binding site. MATII upregulation is inhibited by its reaction product, leading to MATI/III downregulation. Decreased MATI/III: MATII activity ratio, along with increased SAM decarboxylation for polyamine synthesis, results in decreased SAM. Some of the molecular pathways associated with specific cancer phenotypes are evolutionarily conserved, according to previous comparative functional genomics research. Cell cycle regulators (WNT/FZD, PI3K/AKT, and MAPK) and key genes (MAPK, IKK/NF-kB) are upregulated in human and rodent HCC progression. Pseudoprognostic markers for HCC include MAT1A/MAT2A switch. Changes in MAT1A expression and SAM levels occur during hepatocarcinogenesis. No evidence of SAM’s therapeutic effect on HCC has been found. The effects of stable MAT1A overexpression or MAT2A/MAT2B inhibition in vivo should be studied first. MAT2A or MAT2B-silenced HepG2 cells proliferate less in leptin. However, intracellular viral vector transduction in vivo has many limitations. This review interprets recent advances in SAM metabolism deregulation in liver injury predisposing to HCC and determining HCC prognosis.

Differential effect of chronic mild stress on anxiety and depressive-like behaviors in three strains of male and female laboratory mice

Major depressive disorder is the most common psychiatric disorder worldwide. To understand mechanisms and search for new approaches to treating depression, animal models are crucial. Chronic mild stress (CMS) is the most used animal model of depression. Although CMS is considered a robust model of depression, conflicting results have been reported for emotion-related behaviors, which the intrinsic characteristics of each rodent strain could explain. To further shed light on the impact of genetic background on the relevant parameters commonly addressed in depression, we examined the effect of 4-weeks CMS on anxiety and depression-related behaviors and body weight gain in three strain mice (BALB/c, C57BL/6, and CD1) of both sexes. CMS reduced body weight gain in C57BL/6NCrl and CD1 male mice. C57BL/6 animals exhibited a more pronounced anxious-like behavior than CD1 and BALB/c mice in the light-dark box (LDB) and the elevated plus maze (EPM) tests, whereas BALB/c animals exhibited the more robust depressive-like phenotype in the splash test (ST), tail suspension test (TST) and forced-swimming test (FST). Under CMS, exposure did not affect anxiety-related behaviors in any strain but induced depression-like behaviors strain-dependently. CMS C57BL/6 and CD1 mice of both sexes showed depression-like behaviors, and CMS BALB/c male mice exhibited reduced depressive behaviors in the FST. These results suggest a differential effect of stress, with the C57BL/6 strain being more vulnerable to stress than the CD1 and BALB/c strain mice. Furthermore, our findings emphasize the need for researchers to consider mouse strains and behavioral tests in their CMS experimental designs.

Monitoring Infected Reticulocytes During Murine Malaria Infection

Abstract Malaria infection is a major cause of mortality worldwide. According to the 2022 World Health Organization Malaria Report, malaria caused approximately 247 million infections and 619,000 deaths in 2021, with more than 470,000 children dying of malaria. The gold-standard for measuring parasitemia is counting infected red blood cells (RBCs) by eye using Giemsa staining whole blood smears. This method is time consuming and is subject to error by both who is counting, the number of cells counted, and which frames are selected for counting. Automating the process of measuring malaria infection by flow cytometry decreases both the time required to obtain accurate parasitemia counts and the possible error on behalf of the researcher. Hundreds of thousands of cells can be counted by flow cytometry in a shorter period of time. Animal models of malaria infection are widespread and well-characterized. The rodent malaria strain P. berghei has shown preferential infection of reticulocytes over mature RBCs. Here we outline a method of measuring P. berghei blood stage infection in reticulocytes and mature RBCs and comparing the results to Giemsa stained whole blood smears. Using commercially available P. berghei ANKA expressing green-fluorescent protein (GFP), we infected wild type mice with 1x106 parasitized RBCs by intraperitoneal injection. Whole blood samples were collected daily starting day 3 post infection through day 7 by tail vein collection. Random and representative fields of Giemsa stained peripheral smears were selected to measure the percentage of parasitemia in mature RBCs and reticulocytes for a total cell count of approximately 1000. For flow cytometry, whole blood was incubated in 500uL of 1X SYBR Green I Nucleic Acid Gel Stain in PBS at 37°C for 20 minutes in the dark, washed with PBS, and stained with anti-CD71 to label reticulocytes. During the early stages of infection, the reticulocyte percentage of infected animals is not significant from uninfected animals, approximately 1.86%. As parasitemia increases over time, although the percentage of total reticulocytes decreases, the percentage of infected reticulocytes increases. On day 3 through 7 for one experimental replicate, day 3 demonstrated 1.86% total reticulocytes, and of these 2.56% reticulocytes were infected; day 4 had 0.66% total reticulocytes, and of these 32.92% were infected; day 5 showed 0.18% reticulocytes with 71.81% infected reticulocytes; on day 6 there were 0.04% reticulocytes with 75.44% infected reticulocytes; and day 7 had 0.01% reticulocytes with 69.56% infected reticulocytes. There was a strong correlation (R2 = 0.9147) when comparing flow cytometry to measure parasitemia with counting parasitemia by peripheral smear. This flow cytometry panel is an excellent tool to assess malarial infection of reticulocytes compared to mature RBCs and can be applied to other malarial species while decreasing bias, error and time needed to conduct the experiment.

Virtual histology of Alzheimer’s disease: Biometal entrapment within amyloid-[formula omitted] plaques allows for detection via X-ray phase-contrast imaging

Amyloid-β (Aβ) plaques from Alzheimer’s Disease (AD) can be visualized ex vivo in label-free brain samples using synchrotron X-ray phase-contrast tomography (XPCT). However, for XPCT to be useful as a screening method for amyloid pathology, it is essential to understand which factors drive the detection of Aβ plaques. The current study was designed to test the hypothesis that Aβ-related contrast in XPCT could be caused by Aβ fibrils and/or by metals trapped in the plaques. Fibrillar and elemental compositions of Aβ plaques were probed in brain samples from different types of AD patients and AD models to establish a relationship between XPCT contrast and Aβ plaque characteristics. XPCT, micro-Fourier-Transform Infrared spectroscopy and micro-X-Ray Fluorescence spectroscopy were conducted on human samples (one genetic and one sporadic case) and on four transgenic rodent strains (mouse: APPPS1, ArcAβ, J20; rat: TgF344). Aβ plaques from the genetic AD patient were visible using XPCT, and had higher β-sheet content and higher metal levels than those from the sporadic AD patient, which remained undetected by XPCT. Aβ plaques in J20 mice and TgF344 rats appeared hyperdense on XPCT images, while they were hypodense with a hyperdense core in the case of APPPS1 and ArcAβ mice. In all four transgenic strains, β-sheet content was similar, while metal levels were highly variable: J20 (zinc and iron) and TgF344 (copper) strains showed greater metal accumulation than APPPS1 and ArcAβ mice. Hence, a hyperdense contrast formation of Aβ plaques in XPCT images was associated with biometal entrapment within plaques. Statement of significanceThe role of metals in Alzheimer’s disease (AD) has been a subject of continuous interest. It was already known that amyloid-β plaques (Aβ), the earliest hallmark of AD, tend to trap endogenous biometals like zinc, iron and copper. Here we show that this metal accumulation is the main reason why Aβ plaques are detected with a new technique called X-ray phase contrast tomography (XPCT). XPCT enables to map the distribution of Aβ plaques in the whole excised brain without labeling. In this work we describe a unique collection of four transgenic models of AD, together with a human sporadic and a rare genetic case of AD, thus exploring the full spectrum of amyloid contrast in XPCT.

The pharmacokinetic profile of brensocatib and its effect on pharmacodynamic biomarkers including NE, PR3, and CatG in various rodent species.

Brensocatib is a novel, oral, selective, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), which activates several neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG) in the bone marrow during the early stage of neutrophil maturation. These NSPs are associated with pathogen destruction and inflammatory mediation; their dysregulated activation can result in excess secretion of active NSPs causing damaging inflammation and contributing to neutrophil-mediated inflammatory and autoimmune diseases. Pharmacological inhibition of DPP1 in the bone marrow could therefore represent an attractive strategy for these neutrophil-driven diseases. A completed Phase 2 trial in non-cystic fibrosis bronchiectasis patients (ClinicalTrials.gov number NCT03218917; EudraCT number: 2017-002533-32) indeed demonstrated that administration of brensocatib attenuated the damaging effects of chronic inflammation by inhibiting the downstream activation of NSPs. To support a range of preclinical programs and further understand how rodent species and strains may affect brensocatib's pharmacokinetic (PK) profile and its pharmacodynamic (PD) effects on NE, PR3, and CatG, an extensive naïve dosing study with brensocatib at different dosing levels, frequencies, and durations was undertaken. Dose-dependent PK exposure responses (AUC and Cmax) were observed regardless of the rodent species and strain. Overall, mice showed greater reduction in NSP activities compared to rats. Both mice and rats dosed once daily (QD) had equivalent NSP activity reduction compared to BID (twice a day) dosing when the QD dose was 1.5-times the BID daily dose. For both mouse strains, CatG activity was reduced the most, followed by NE, then PR3; whereas, for both rat strains, PR3 activity was reduced the most, followed by CatG, and then NE. Maximum reduction in NSP activities was observed after ∼7 days and recoveries were nearly symmetrical. These results may facilitate future in vivo brensocatib study dosing considerations, such as the timing of prophylactic or therapeutic administration, choice of species, dosage and dosing frequency.

Sex-related differences in retinal function in Wistar rats: implications for toxicity and safety studies.

Introduction: Wistar Han rats are a preferred strain of rodents for general toxicology and safety pharmacology studies in drug development. In some of these studies, visual functional tests that assess for retinal toxicity are included as an additional endpoint. Although the influence of gender on human retinal function has been documented for more than 6decades, preclinically it is still uncertain if there are differences in retinal function between naïve male and female Wistar Han rats. Methods: In this study, sex-related differences in the retinal function were quantified by analyzing electroretinography (ERG) in 7-9-week-old (n = 52 males and 51 females) and 21-23-week-old Wistar Han rats (n = 48 males and 51 females). Optokinetic tracking response, brainstem auditory evoked potential, ultrasonic vocalization and histology were tested and evaluated in a subset of animals to investigate the potential compensation mechanisms of spontaneous blindness. Results/Discussion: Absence of scotopic and photopic ERG responses was found in 13% of 7-9-week-old (7/52) and 19% of 21-23-week-old males (9/48), but none of female rats (0/51). The averaged amplitudes of rod- and cone-mediated ERG b-wave responses obtained from males were significantly smaller than the amplitudes of the same responses from age-matched females (-43% and -26%, respectively) at 7-9weeks of age. There was no difference in the retinal and brain morphology, brainstem auditory responses, or ultrasonic vocalizations between the animals with normal and abnormal ERGs at 21-23weeks of age. In summary, male Wistar Han rats had altered retinal responses, including a complete lack of responses to test flash stimuli (i.e., blindness), when compared with female rats at 7-9 and 21-23weeks of age. Therefore, sex differences should be considered when using Wistar Han rats in toxicity and safety pharmacology studies with regards to data interpretation of retinal functional assessments.

Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience.

The key element of dopamine (DA) neurotransmission is undoubtedly DA transporter (DAT), a transmembrane protein responsible for the synaptic reuptake of the mediator. Changes in DAT's function can be a key mechanism of pathological conditions associated with hyperdopaminergia. The first strain of gene-modified rodents with a lack of DAT were created more than 25 years ago. Such animals are characterized by increased levels of striatal DA, resulting in locomotor hyperactivity, increased levels of motor stereotypes, cognitive deficits, and other behavioral abnormalities. The administration of dopaminergic and pharmacological agents affecting other neurotransmitter systems can mitigate those abnormalities. The main purpose of this review is to systematize and analyze (1) known data on the consequences of changes in DAT expression in experimental animals, (2) results of pharmacological studies in these animals, and (3) to estimate the validity of animals lacking DAT as models for discovering new treatments of DA-related disorders.

Abstract 42: In vivo subcutaneous and orthotopic cancer xenograft modeling in the SRG immunodeficient rat

Abstract Human cancer xenografts are a vital tool for understanding tumor biology, growth kinetics, and therapeutic efficacy using animal models. Historically, immunodeficient mice have been the standard rodent species for cancer xenograft modeling. However, an immunodeficient rat that supports a wide variety of human cancer cell types would provide a larger rodent strain for easier surgical manipulation, serial blood sampling, and provide a single model in which efficacy, pharmacokinetics, and toxicology can be performed. We have created a Sprague Dawley Rag2 -/-, Il2rg -/- rat (SRGTM OncoRat®) that provides a highly supportive environment for growing tumors of human origin. The SRG rat lacks B, T, and NK cells and readily supports the growth of multiple human cancer cell lines. The SRG rat is more immunodeficient than the Nude rat, suggesting it may be permissive to a wider variety of human cancer types. Here we demonstrate the utility of the SRG rat for both subcutaneous and orthotopic xenograft modeling. The SRG rat supports the growth of both lung and liver orthotopic cancers. In addition, the SRG rat supports the growth of orthoptic human glioblastoma multiforme in the brain. We use in vivo imaging to visualize tumor establishment and growth in subcutaneous, orthotopic, and metastatic models. Furthermore, our data show the ability of the SRG rat to support the growth of multiple different human cancer cell types subcutaneously in two different matrices, Matrigel® and VitroGel®. These data confirm that the SRG rat is an excellent host for studying human cancer. Our data demonstrate that the SRG rat has a high utility for studies using in vivo imaging, orthotopic tumor implantation, and standard subcutaneous tumor modeling. As the most immunodeficient rat commercially available, the SRG rat supports the growth of multiple human cancer types in a larger rodent strain relative to commercially available mouse models. Citation Format: Diane Begemann, Aida Javidan, Cynthia Dunn, Nicolas Johnston, R. Grace Walton, Valeriya Steffey, Ian Corbin, Niveen Fulcher, Cleusa De Oliveira, Hu Xu, Mila Uzelac, Andrew Deweyert, John A. Ronald, Susanne Schmid, Matthew O. Hebb, Fallon K. Noto. In vivo subcutaneous and orthotopic cancer xenograft modeling in the SRG immunodeficient rat [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 42.

Nonshivering thermogenesis revisited: sympathetic and non-sympathetic contributions

Factors of diet and environment contribute to complementary, additive mechanisms that influence the magnitude of diet induced thermogenesis generated in man and animals. Both short terms sympathetically mediated and longer acting thyroidal mediated pathways have been identified and appear to function in a metabolically coordinated fashion to facilitate biochemical and physiologic pathways of energy balance implicating multiple organs and peripheral tissues during periods of over- and under-nutrition. In a congenic lean rodent model known to express parameters of environmentally and diet induced mediated thermogenesis, thyroidal and sympathetic contributions each contributed to approximately 50% of the relative increase in VO2 in quietly resting animals after consuming a high energy palatable diet as determined in the presence vs. absence of α-methylparatyrosine, a sympathoplegic chemical agent. In contrast, in the obese phenotype of the corpulent and other rodent strains, both sympathetic and thyroidal contributions to adaptive thermogenic mechanisms are impaired in response to both nutritional and environmental challenge, contributing to a greater efficiency of energy metabolism and body fat accretion. Thus, the purpose of the present review is to approximate the qualitative distribution between the two primary factors linked to the physiologic process resulting in the expression of diet induced thermogenesis in a normally lean phenotype of rat, the LA/Ntul//-cp.

Why use a biobank? Sharing mutations, gene editing and navigating the COVID-19 pandemic.

Cryopreservation is seen as a key aspect of good colony management, which supports the drive towards improvements in animal care and the implementation of the 3Rs. However, following the advent of gene editing technologies, the generation of new rat and mouse models is quicker and cheaper than ever before. This has led some to question the future value of biobanks around the world. In the following commentary we argue that the need to cryopreserve rat and mouse strains and distribute them from well-funded repositories is as strong as it has ever been. Repositories should not be considered as simply collections of redundant model organisms. Biobanks have a vital role to play in good experimental design. They distribute identical, quality controlled mutant strains to the community and eliminate the need to recreate mice. Archived material provides a check point in the development of new strains of rodents that minimises genetic drift and breeding failures. Cryopreservation also makes resource sharing easier and cheaper, and improves animal care by eliminating the need for live animal shipments. Furthermore, routine cryopreservation of valuable strains protects them from unforeseen events, such as the SARS and COVID-19 pandemics, which were accompanied by the very real prospect of immediate lab closures and/or severe disruption to courier services, rendering live animal shipments non-viable.

Male or female sex: considerations and translational aspects in diabetic foot ulcer research using rodent models.

Treatment of nonhealing diabetic foot ulcers (DFUs) is a major clinical concern and challenge for clinicians. Despite the advancement in treatment strategies, there is no definitive treatment for complicated nonhealing DFUs. Animal models are crucial for understanding pathogenesis and investigating novel therapeutic small molecules and the rodent model is commonly used for research related to cutaneous wound healing. Sexual dimorphism and its effect on the efficacy of sex hormones in enhancing healing in cutaneous wounds using a rodent model have been discussed, however, there is a lack of data related to diabetic foot ulcers. Further, the effects of sexual dimorphism on the issues related to induction of diabetes, differential immune response, type and size of the wound, the effectiveness of topical versus systemic treatment, and molecular mechanisms involved in wound healing like hemostasis, granulation tissue formation, the response of keratinocytes and fibroblasts, inflammation, and skin anatomy are scarcely discussed. Understanding these aspects is of significance and will help in choosing the correct sex, species, and strain of rodents while investigating therapeutic small molecules for DFUs. This review critically summarized these issues and their translational aspects followed by highlighting the effect of sexual dimorphism on these important aspects.

A comprehensive approach to modeling maternal immune activation in rodents.

Prenatal brain development is a highly orchestrated process, making it a very vulnerable window to perturbations. Maternal stress and subsequent inflammation during pregnancy leads to a state referred to as, maternal immune activation (MIA). If persistent, MIA can pose as a significant risk factor for the manifestation of neurodevelopmental disorders (NDDs) such as autism spectrum disorder and schizophrenia. To further elucidate this association between MIA and NDD risk, rodent models have been used extensively across laboratories for many years. However, there are few uniform approaches for rodent MIA models which make not only comparisons between studies difficult, but some established approaches come with limitations that can affect experimental outcomes. Here, we provide researchers with a comprehensive review of common experimental variables and potential limitations that should be considered when designing an MIA study based in a rodent model. Experimental variables discussed include: innate immune stimulation using poly I:C and LPS, environmental gestational stress paradigms, rodent diet composition and sterilization, rodent strain, neonatal handling, and the inclusion of sex-specific MIA offspring analyses. We discuss how some aspects of these variables have potential to make a profound impact on MIA data interpretation and reproducibility.

The origins, isolation, and biological characterization of rodent malaria parasites.

Rodent malaria parasites have been widely used in all aspects of malaria research to study parasite development within rodent and insect hosts, drug resistance, disease pathogenesis, host immune response, and vaccine efficacy. Rodent malaria parasites were isolated from African thicket rats and initially characterized by scientists at the University of Edinburgh, UK, particularly by Drs. Richard Carter, David Walliker, and colleagues. Through their efforts and elegant work, many rodent malaria parasite species, subspecies, and strains are now available. Because of the ease of maintaining these parasites in laboratory mice, genetic crosses can be performed to map the parasite and host genes contributing to parasite growth and disease severity. Recombinant DNA technologies are now available to manipulate the parasite genomes and to study gene functions efficiently. In this chapter, we provide a brief history of the isolation and species identification of rodent malaria parasites. We also discuss some recent studies to further characterize the different developing stages of the parasites including parasite genomes and chromosomes. Although there are differences between rodent and human malaria parasite infections, the knowledge gained from studies of rodent malaria parasites has contributed greatly to our understanding of and the fight against human malaria.

Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives.

Animal models of epilepsy are of great importance in epileptology. They are used to study the mechanisms of epileptogenesis, and search for new genes and regulatory pathways involved in the development of epilepsy as well as screening new antiepileptic drugs. Today, many methods of modeling epilepsy in animals are used, including electroconvulsive, pharmacological in intact animals, and genetic, with the predisposition for spontaneous or refractory epileptic seizures. Due to the simplicity of manipulation and universality, genetic models of audiogenic epilepsy in rodents stand out among this diversity. We tried to combine data on the genetics of audiogenic epilepsy in rodents, the relevance of various models of audiogenic epilepsy to certain epileptic syndromes in humans, and the advantages of using of rodent strains predisposed to audiogenic epilepsy in current epileptology.

Addiction-like behaviour towards high-fat high-sugar food predicts relapse propensity in both obesity prone and obesity resistant C57BL/6 J mice

Compulsive overeating of palatable food is thought to underlie some forms of obesity. Similarities are often observed in the behavioural symptomology and the neuropathophysiology underlying substance use disorder and compulsive overeating. As such, preclinical animal models which assess addiction-like behaviour towards food may assist the understanding of the neurobiology underlying overeating behaviour. Further, the relationship between these behaviours and the propensity for diet-induced obesity warrants examination. In this study we investigated the relationship between the propensity for diet-induced obesity (DIO) and addiction-like behaviour towards highly palatable food in C57BL/6 J mice as measured by a 3-criteria model. We also examined the extent to which performance on this 3-criteria model predicted two key hallmark features of addiction – resistance to extinction and relapse propensity (as measured by reinstatement of lever pressing). C57BL/6 J mice were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions whereby addiction-like behaviour towards a high-fat high-sugar food reward was assessed using a 3-criteria model similar to that used to assess addiction-like behaviour towards drugs of abuse. In contrast to findings in rats, no difference in addiction-like behaviour towards food was observed between obesity prone (OP) and obesity resistant (OR) mice. Similarly, principal components analysis found no distinct patterns in the relationship between addiction-like behaviours across treatment groups. This suggests that the strain and species of rodent may be critical for studying the mechanisms underlying pathological overconsumption. Further analysis revealed that the extent of performance on the 3-criteria model correlated with the propensity for C57BL/6 J mice to both extinguish food seeking behaviour and “relapse” after a period of withdrawal. This finding was evident across all groups, regardless of DIO. Collectively, these data validate the 3-criteria model as a robust model to comprehensively assess food addiction-like behaviour in mice, regardless of prior food intake history.

Comparative Study of The Effects of Confounding Factors on Improving Rat Pancreatic Islet Isolation Yield and Quality.

Objective Isolated pancreatic islets are valuable resources for a wide range of research, including cell replacement studies and cell-based platforms for diabetes drug discovery and disease modeling. Islet isolation is a complex and stepwise procedure aiming to obtain pure, viable, and functional islets for in vitro and in vivo studies. It should be noted that differences in rodent strains, gender, weight, and density gradients may affect the isolated islet’s properties. We evaluated the variables affecting the rat islet isolation procedure to reach the maximum islet yield and functionality, which would be critical for further studies on islet regenerative biology. Materials and Methods The present experimental study compared the yield and purity of isolated islets from non- diabetic rats of two different strains. Next, islet particle number (IPN) and islet equivalent (IEQ) were compared between males and females, and the weight range that yields the highest number of islets was investigated. Moreover, the influence of three different density gradients, namely Histopaque, Pancoll, and Lymphodex, on final isolated islets purity and yield were assessed. Finally, the viability and functionality of isolated islets were measured. Results The IEQ, IPN, and purity of isolated islets in 15 Lister hooded rats (LHRs) were significantly (P≤0.05) higher than those of the other strains. Male LHRs resulted in significantly higher IEQ compared to females (P≤0.05). Moreover, IPN and IEQ did not significantly vary among different weight groups. Also, the utilization of Histopaque and Pancoll leads to higher yield and purity. In vivo assessments of the isolated islets presented significantly reduced blood glucose percentage in the transplanted group on days 2-5 following transplantation. ConclusionBased on these results, an optimal protocol for isolating high-quality rat islets with a constant yield, purity, and function has been established as an essential platform for developing diabetes research.