The prenatal use of agmatine prevents social behavior deficits in VPA-exposed mice by activating the ERK/CREB/BDNF signaling pathway.

BACKGROUND: According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid. METHODS: In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring. RESULTS: The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway. CONCLUSION: Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.

Space wandering in the rodent default mode network.

The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here, we use multisite GCaMP (a genetically encoded calcium indicator) fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes-the retrosplenial cortex, cingulate cortex, and prelimbic cortex-as well as the anterior insula node of the salience network, and their association with the rats' spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and found that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a "task-negative" network disengaged from the external world. By illuminating the DMN's role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts.

Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain.

Objective.Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable for all types of chronic pain. Direct current (DC) stimulation is a recently developed technology which affects small-diameter fibres more strongly than pulsatile stimulation. Since nociceptors are predominantly small-diameter Aδand C fibres, we investigated if this property could be applied to preferentially reduce nociceptive signalling.Approach.We applied a DC waveform to the sciatic nerve in rats of both sexes and recorded multi-unit spinal activity evoked at the hindpaw using various natural stimuli corresponding to different sensory modalities rather than broad-spectrum electrical stimulus. To determine if DC neuromodulation is effective across different types of chronic pain, tests were performed in models of neuropathic and inflammatory pain.Main results.We found that in both pain models tested, DC application reduced responses evoked by noxious stimuli, as well as tactile-evoked responses which we suggest may be involved in allodynia. Different spinal activity of different modalities were reduced in naïve animals compared to the pain models, indicating that physiological changes such as those mediated by disease states could play a larger role than previously thought in determining neuromodulation outcomes.Significance.Our findings support the continued development of DC neuromodulation as a method for reduction of nociceptive signalling, and suggests that it may be effective at treating a broader range of aberrant pain conditions than existing devices.

Ibrutinib disrupts blood-tumor barrier integrity and prolongs survival in rodent glioma model.

In malignant glioma, cytotoxic drugs are often inhibited from accessing the tumor site due to the blood-tumor barrier (BTB). Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown to independently impair aortic endothelial adhesion and increase rodent glioma model survival in combination with cytotoxic therapy. Yet additional research is required to understand ibrutinib's effect on BTB function. In this study, we detail baseline BTK expression in glioma cells and its surrounding vasculature, then measure endothelial junctional expression/function changes with varied ibrutinib doses in vitro. Rat glioma cells and rodent glioma models were treated with ibrutinib alone (1-10 µM and 25 mg/kg) and in combination with doxil (10-100 µM and 3 mg/kg) to assess additive effects on viability, drug concentrations, tumor volume, endothelial junctional expression and survival. We found that ibrutinib, in a dose-dependent manner, decreased brain endothelial cell-cell adhesion over 24 h, without affecting endothelial cell viability (p < 0.005). Expression of tight junction gene and protein expression was decreased maximally 4 h after administration, along with inhibition of efflux transporter, ABCB1, activity. We demonstrated an additive effect of ibrutinib with doxil on rat glioma cells, as seen by a significant reduction in cell viability (p < 0.001) and increased CNS doxil concentration in the brain (56 ng/mL doxil alone vs. 74.6 ng/mL combination, p < 0.05). Finally, Ibrutinib, combined with doxil, prolonged median survival in rodent glioma models (27 vs. 16 days, p < 0.0001) with brain imaging showing a - 53% versus - 75% volume change with doxil alone versus combination therapy (p < 0.05). These findings indicate ibrutinib's ability to increase brain endothelial permeability via junctional disruption and efflux inhibition, to increase BTB drug entry and prolong rodent glioma model survival. Our results motivate the need to identify other BTB modifiers, all with the intent of improving survival and reducing systemic toxicities.

Health of Holochilus chacarius (Rodentia: Cricetidae) in rice agroecosystem in a neotropical wetland assessed by histopathology.

Small mammals have a short lifetime and are strictly associated with their environment. This work aimed to use histopathology to assess the health of Holochilus chacarius in a rice agroecosystem in the Pantanal of Mato Grosso do Sul. During necropsy, fragments of the lung, kidney, skin, liver, and reproductive system of 33 animals were collected and submitted to histological processing. Tissue damages were evaluated as mild, moderate, and severe and arranged in a matrix for further statistical analysis. Furthermore, we used generalized linear models to verify the influence of tissue changes on the body condition, obtained by a regression between body mass and length. In the lungs, we found an intense inflammatory infiltrate associated with anthracosis that had a negative influence on the body's condition. Also, we observed degenerative and inflammatory changes in the liver, kidneys, skin, and reproductive system that ranged from mild to moderate. The histopathological lesions observed in this study may be associated with environmental alterations of anthropic origin such as the exposure to soot from wildfires and heavy metals, evidenced by lesions in the lung, kidney, and liver. The present study provided a histopathological matrix as a new approach that allows to classify and quantify the tissue alterations. Tissue changes when associated with body condition demonstrated to be an effective tool to assess the health of small free-living mammals, showing that these animals can be used as bioindicators of environmental condition.

Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders.

Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.

Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception-Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been recognized as important mediators in migraine but their mechanisms of action and interaction have not been fully elucidated. Monoclonal anti-CGRP antibodies like fremanezumab are successful preventives of frequent migraine and can be used to study CGRP actions in preclinical experiments. Fremanezumab (30 mg/kg) or an isotype control monoclonal antibody was subcutaneously injected to Wistar rats of both sexes. One to several days later, glyceroltrinitrate (GTN, 5 mg/kg) mimicking nitric oxide (NO) was intraperitoneally injected, either once or for three consecutive days. The trigeminal ganglia were removed to determine the concentration of CGRP using an enzyme-linked immunosorbent assay (ELISA). In one series of experiments, the animals were trained to reach an attractive sugar solution, the access to which could be limited by mechanical or thermal barriers. Using a semi-automated registration system, the frequency of approaches to the source, the residence time at the source, and the consumed solution were registered. The results were compared with previous data of rats not treated with GTN. The CGRP concentration in the trigeminal ganglia was generally higher in male rats and tended to be increased in animals treated once with GTN, whereas the CGRP concentration decreased after repetitive GTN treatment. No significant difference in CGRP concentration was observed between animals having received fremanezumab or the control antibody. Animals treated with GTN generally spent less time at the source and consumed less sugar solution. Without barriers, there was no significant difference between animals having received fremanezumab or the control antibody. Under mechanical barrier conditions, all behavioral parameters tended to be reduced but animals that had received fremanezumab tended to be more active, partly compensating for the depressive effect of GTN. In conclusion, GTN treatment seems to increase the production of CGRP in the trigeminal ganglion independently of the antibodies applied, but repetitive GTN administration may deplete CGRP stores. GTN treatment generally tends to suppress the animals' activity and increase facial sensitivity, which is partly compensated by fremanezumab through reduced CGRP signaling. If CGRP and NO signaling share the same pathway in sensitizing trigeminal afferents, GTN and NO may act downstream of CGRP to increase facial sensitivity.

Prevalence, genetic diversity and eco-epidemiology of pathogenic Leptospira species in small mammal communities in urban parks Lyon city, France.

Rodents are recognized as the main reservoirs of Leptospira spp. Rats, in particular, serve as hosts for the widely predominant Leptospira interrogans serovar Icterohaemorrhagiae, found worldwide. Several studies have shown the importance of other reservoirs, such as mice or hedgehogs, which harbor other leptospires' serovars. Nevertheless, our knowledge of circulating Leptospira spp. in reservoirs other than rats remains limited. In this context, we proposed an eco-health approach to assess the health hazard associated with leptospires in urban green spaces, where contacts between human/small mammals and domestic animals are likely. We studied the prevalence, the diversity of circulating strains, and epidemiology of pathogenic Leptospira species in small terrestrial mammal communities (rodents and shrews), between 2020-2022, in two parks in Lyon metropolis, France. Our study showed a significant carriage of Leptospira spp. in small terrestrial mammals in these parks and unveiled a global prevalence rate of 11.4%. Significant variations of prevalence were observed among the small mammal species (from 0 to 26.1%), with Rattus norvegicus exhibiting the highest infection levels (26.1%). We also observed strong spatio-temporal variations in Leptospira spp. circulation in its reservoirs. Prevalence seems to be higher in the peri-urban park and in autumn in 2021 and 2022. This is potentially due to differences in landscape, abiotic conditions and small mammal communities' composition. Our study suggests an important public health relevance of rats and in a lesser extent of other rodents (Apodemus spp., Clethrionomys glareolus and Mus musculus) as reservoirs of L. interrogans, with rodent species carrying specific serogroups/serovars. We also emphasize the potential hazard associated between the shrew Crocidura russula and L. kirschneri. Altogether, these results improve our knowledge about the prevalence of leptospirosis in an urban environment, which is an essential prerequisite for the implementation of prevention of associated risks.

Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma.

Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.

Optimizing semen cryopreservation in Calomys laucha: a step forward in rodent reproductive research.

BACKGROUND: Examining semen cryopreservation in Calomys laucha offers valuable insights for reproductive research and species conservation. OBJECTIVE: To determine the most effective sugar for the cryopreservation of C. laucha semen. MATERIALS AND METHODS: Using 36 epididymides from C. laucha, semen samples were diluted in a 3% skimmed milk medium supplemented with one of four sugars (glucose, fructose, lactose, or sucrose) at a concentration of 0.3 M. These mixtures underwent a conditioning phase at 37 degree C for 10 min, cooled to -80 degree C for another 10 min, and were subsequently stored in liquid nitrogen. RESULTS: Upon thawing, samples treated with lactose and glucose solutions show superior sperm motility, achieving 8.2% and 10.0% respectively, in contrast to the fructose (2.0%) and sucrose (4.1%) mixtures. Furthermore, samples preserved in glucose registered the highest sperm penetration rates, reaching 44.9%. CONCLUSION: Our findings suggest that a cryopreservation medium containing 0.3 M glucose can contribute to the safeguarding C. laucha rodent semen. https://doi.org/10.54680/fr24210110612.

Homeobox gene-encoded transcription factors in development and mature circadian function of the rodent pineal gland.

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene-encoded transcription factors in developmental and circadian mature neuroendocrine function.

No evidence tube entrapment distresses rodents in typical empathy tests.

In the first two experiments an empty tube open at one end was placed in different locations. Male hamsters, tested one at a time, tended to stay close to the tube or in it. During the first minute of the first 4 sessions of Experiment 3, the hamster was unrestrained. If it entered the tube, it was locked within the tube. If it did not enter the tube during the first min, it was placed in it, and the tube was locked. Fifteen min later, the tube was opened, and the hamster was unrestrained for a further 20 min. The tube remained open during Session 5. Hamsters spent more time near the tube than predicted by chance and continued to enter the tube although tube-occupancy duration did not differ from chance levels. In Experiment 4, male rats were tested in two groups: rats in one group had been previously trapped in a tube and rats in the other group allowed to freely explore the test space. For the first two min of each of four 20-min sessions, trapped-group subjects were permitted to move about the chamber unless they entered the tube. In that case, they were locked in for the remainder of the session. If, after two min, they did not enter the tube, they were locked in it for the remaining 18 min. Free rats were unrestricted in all sessions. In Session 5, when both groups were permitted to move freely in the chamber, trapped and free rats spent more time in and near the tube than predicted by chance. These data show tube restraint does not seem to distress either hamsters or rats.

Impact of light-emitting diodes on visual cortex layer 5 pyramidal neurons (V1-L5PNs)-A rodent study.

Purpose: Light-induced neural retinal insult leads to alterations in the visual cortex neurons. We examined light-induced neuronal alterations in the visual cortex layer 5 pyramidal neurons (V1-L5PNs) of adult male Wistar rats. Methods: A total of 24 rats were divided into the following groups (n=6 each): control (NC), blue (BL), white (WL), and yellow (YL). The exposure groups were subjected to light-emitting diodes (LED) exposure (450-500 lx) of differing wavelengths for 90 days (12:12 16 light-dark cycle). After LED exposure, the animals were sacrificed, and the brain tissues were removed and impregnated in freshly prepared Golgi-Cox stain for 21 days. Sholl's grading analysis was used to quantify the apical and basal dendritic branching points and intersections of the V1-L5PNs. Results: There was a significant difference in the number of apical branching points among all groups (p<0.001), with a particularly notable difference between the BL and WL groups (p<0.001). A post hoc test revealed that all exposure groups (BL, WL, and YL) had fewer apical branching points (p<0.001) on an average of 3.6 µm and a significant reduction in the dendritic intersections (p<0.001) compared to the number of branching points extending from layer Va (V1) neurons. Conclusions: Chronic and cumulative exposure to blue and white LEDs led to the pruning of V1-L5PNs, which might impair visual processing.

Molecular epidemiological study of Scrub Typhus in residence, farm and forest habitats from Yunnan Province, China.

The number of people suffering from scrub typhus, which is not of concern, is increasing year by year, especially in Yunnan Province, China. From June 1, 2021 to August 15, 2022, a total of 505 mammalian samples were collected from farm, forest, and residential habitats with high incidence of scrub typhus in Yunnan, China, for nPCR (nested PCR) and qPCR (quantitative real-time PCR) detection of Orientia tsutsugamushi. A total of 4 orders of murine-like animals, Rodentia (87.52%, n = 442), Insectivora (10.29%, n = 52), Lagomorpha (1.79%, n = 9) and Scandentia (0.40%, n = 2) were trapped. Comparing the qPCR infection rates in the three habitats, it was no significant difference that the infection rate of residential habitat (44.44%) and that of the farm habitat (45.05%, P>0.05), which is much larger than that of the forest habitat (3.08%) (P<0.001). Three genotypes (Karp-like, Kato-like and TA763-like) of O. tsutsugamushi were found from Yunnan, China in this study.

Substantial viral diversity in bats and rodents from East Africa: insights into evolution, recombination, and cocirculation.

BACKGROUND: Zoonotic viruses cause substantial public health and socioeconomic problems worldwide. Understanding how viruses evolve and spread within and among wildlife species is a critical step when aiming for proactive identification of viral threats to prevent future pandemics. Despite the many proposed factors influencing viral diversity, the genomic diversity and structure of viral communities in East Africa are largely unknown. RESULTS: Using 38.3 Tb of metatranscriptomic data obtained via ultradeep sequencing, we screened vertebrate-associated viromes from 844 bats and 250 rodents from Kenya and Uganda collected from the wild. The 251 vertebrate-associated viral genomes of bats (212) and rodents (39) revealed the vast diversity, host-related variability, and high geographic specificity of viruses in East Africa. Among the surveyed viral families, Coronaviridae and Circoviridae showed low host specificity, high conservation of replication-associated proteins, high divergence among viral entry proteins, and frequent recombination. Despite major dispersal limitations, recurrent mutations, cocirculation, and occasional gene flow contribute to the high local diversity of viral genomes. CONCLUSIONS: The present study not only shows the landscape of bat and rodent viromes in this zoonotic hotspot but also reveals genomic signatures driven by the evolution and dispersal of the viral community, laying solid groundwork for future proactive surveillance of emerging zoonotic pathogens in wildlife. Video Abstract.

Histological Analysis of Trophoblast Cells in the Mouse Placental Labyrinth Zone.

The mouse is a common animal species used for translational studies. In reproductive studies, this animal is typically preferred over other models as the rodent placenta shows similarities to the human but has a relatively short gestational period. In mice, the transport of oxygen and nutrients between mother and fetus occurs in a restricted area of the placenta called the labyrinth zone. Here, we provide a detailed protocol to study labyrinth zone trophoblast proliferation and syncytial trophoblast identification using paraffin-embedded histological sections of the mouse placenta and immunohistochemistry. By describing step by step how to collect the mouse placenta and process and analyze the labyrinth zone, we hope to help other scientists understand the contribution of changes in placental transport function in their experimental model and therefore advance our understanding of mechanisms underlying pregnancy complications.

Integration of in vivo electrophysiology and optogenetics in rodents with PEDOT:PSS neural electrode array.

Here, we present a protocol for the fabrication of transparent implantable electrode arrays for integrating optogenetics and electrophysiology. We describe steps for fabricating microelectrodes using the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). We then detail procedures for analyzing performance of the electrodes and recording light-evoked neural activities from the transgenic mouse. This protocol utilizes photolithography rather than conventional electrodeposition. For complete details on the use and execution of this protocol, please refer to Cho et al. (2022).1.

Eutrichophilus cordiceps Mjöberg, 1910 (Ischnocera: Trichodectidae) in Spiny Tree Porcupines (Coendou villosus): New locality records and the first molecular evidence of association with Bartonella sp.

The chewing louse genus Eutrichophilus Mjöberg has 19 species only associated with porcupines (Rodentia: Erethizontidae). Of these species, E. cercolabes, E. cordiceps, E. emersoni, E. minor, E. moojeni, and E. paraguayensis have been recorded in Brazil. In the present study, we report E. cordiceps for the first time in the São Paulo State (Bauru Municipality) and for the second time in the Santa Catarina State (Lages Municipality), providing scanning electron images and light microscopy for the eggs, as well as the first molecular data (18S rRNA) for the genus. Additionally, Bartonella sp. was detected for the first time in this chewing lice species.

Comparative analysis of human, rodent and snake deltavirus replication.

The recent discovery of Hepatitis D (HDV)-like viruses across a wide range of taxa led to the establishment of the Kolmioviridae family. Recent studies suggest that kolmiovirids can be satellites of viruses other than Hepatitis B virus (HBV), challenging the strict HBV/HDV-association dogma. Studying whether kolmiovirids are able to replicate in any animal cell they enter is essential to assess their zoonotic potential. Here, we compared replication of three kolmiovirids: HDV, rodent (RDeV) and snake (SDeV) deltavirus in vitro and in vivo. We show that SDeV has the narrowest and RDeV the broadest host cell range. High resolution imaging of cells persistently replicating these viruses revealed nuclear viral hubs with a peculiar RNA-protein organization. Finally, in vivo hydrodynamic delivery of viral replicons showed that both HDV and RDeV, but not SDeV, efficiently replicate in mouse liver, forming massive nuclear viral hubs. Our comparative analysis lays the foundation for the discovery of specific host factors controlling Kolmioviridae host-shifting.

Microbiome diversity and zoonotic bacterial pathogen prevalence in Peromyscus mice from agricultural landscapes and synanthropic habitat.

Rodents are key reservoirs of zoonotic pathogens and play an important role in disease transmission to humans. Importantly, anthropogenic land-use change has been found to increase the abundance of rodents that thrive in human-built environments (synanthropic rodents), particularly rodent reservoirs of zoonotic disease. Anthropogenic environments also affect the microbiome of synanthropic wildlife, influencing wildlife health and potentially introducing novel pathogens. Our objective was to examine the effect of agricultural development and synanthropic habitat on microbiome diversity and the prevalence of zoonotic bacterial pathogens in wild Peromyscus mice to better understand the role of these rodents in pathogen maintenance and transmission. We conducted 16S amplicon sequencing on faecal samples using long-read nanopore sequencing technology to characterize the rodent microbiome. We compared microbiome diversity and composition between forest and synanthropic habitats in agricultural and undeveloped landscapes and screened for putative pathogenic bacteria. Microbiome richness, diversity, and evenness were higher in the agricultural landscape and synanthropic habitat compared to undeveloped-forest habitat. Microbiome composition also differed significantly between agricultural and undeveloped landscapes and forest and synanthropic habitats. We detected overall low diversity and abundance of putative pathogenic bacteria, though putative pathogens were more likely to be found in mice from the agricultural landscape. Our findings show that landscape- and habitat-level anthropogenic factors affect Peromyscus microbiomes and suggest that landscape-level agricultural development may be important to predict zoonotic pathogen prevalence. Ultimately, understanding how anthropogenic land-use change and synanthropy affect rodent microbiomes and pathogen prevalence is important to managing transmission of rodent-borne zoonotic diseases to humans.